PMC:1064873 / 24274-25678
Annnotations
LappsTest
{"project":"LappsTest","denotations":[{"id":"T22089","span":{"begin":1388,"end":1393},"obj":"Protein"},{"id":"T22088","span":{"begin":1362,"end":1367},"obj":"Protein"},{"id":"T22087","span":{"begin":1314,"end":1319},"obj":"Protein"},{"id":"T22086","span":{"begin":1130,"end":1134},"obj":"Protein"},{"id":"T22085","span":{"begin":1087,"end":1091},"obj":"Protein"},{"id":"T22084","span":{"begin":1043,"end":1060},"obj":"Protein"},{"id":"T22083","span":{"begin":1009,"end":1014},"obj":"Protein"},{"id":"T22082","span":{"begin":968,"end":975},"obj":"Protein"},{"id":"T22081","span":{"begin":930,"end":935},"obj":"Protein"},{"id":"T22080","span":{"begin":899,"end":903},"obj":"Protein"},{"id":"T22079","span":{"begin":871,"end":875},"obj":"Protein"},{"id":"T22078","span":{"begin":839,"end":844},"obj":"Protein"},{"id":"T22077","span":{"begin":825,"end":830},"obj":"Protein"},{"id":"T22076","span":{"begin":795,"end":799},"obj":"Protein"},{"id":"T22075","span":{"begin":782,"end":787},"obj":"Protein"},{"id":"T22074","span":{"begin":727,"end":732},"obj":"Protein"},{"id":"T22073","span":{"begin":707,"end":711},"obj":"Protein"},{"id":"T22072","span":{"begin":668,"end":675},"obj":"Protein"},{"id":"T22071","span":{"begin":645,"end":650},"obj":"Protein"},{"id":"T22070","span":{"begin":603,"end":608},"obj":"Protein"},{"id":"T22069","span":{"begin":585,"end":590},"obj":"Protein"},{"id":"T22068","span":{"begin":549,"end":556},"obj":"Protein"},{"id":"T22067","span":{"begin":516,"end":520},"obj":"Protein"},{"id":"T22066","span":{"begin":421,"end":426},"obj":"Protein"},{"id":"T22065","span":{"begin":356,"end":363},"obj":"Protein"},{"id":"T22064","span":{"begin":227,"end":256},"obj":"Protein"},{"id":"T22063","span":{"begin":194,"end":207},"obj":"Protein"},{"id":"T22062","span":{"begin":143,"end":148},"obj":"Protein"},{"id":"T22061","span":{"begin":0,"end":5},"obj":"Protein"}],"text":"IL-10 plays a predominant role in limiting immune and inflammatory responses by regulating the function of both macrophages and Th1 cells [1]. IL-10 inhibits the tyrosine phosphorylation of the CD28 molecule and the subsequent phosphatidylinositol 3-kinase binding in T cells, and thereby directly acts on T cells [24]. In the present study, we found that PB CD4+ T cells from patients with active RA, in the presence of IL-10, are able to produce higher levels of IFN-γ after CD3 and CD28 costimulation than normal CD4+ T cells. Despite high-level IL-10R1 expression and constitutive STAT3 activation, IL-10-induced tyrosine phosphorylation of STAT3 is suppressed in RA CD4+ T cells, in contrast to normal CD4+ T cells, where STAT3 phosphorylation is dose-dependently inducible by IL-10. Serum IL-6 from RA patients induces STAT3 but not STAT1 phosphorylation in normal CD4+ T cells, and exogenous IL-6 induces the resistance to IL-10 inhibition of IFN-γ production. RA CD4+ T cells contain higher levels of SOCS1 but contain lower levels of SOCS3 transcripts in comparison with normal CD4+ T cells. These findings indicate that CD4+ T cells become resistant to the inhibitory effect of IL-10 before migration into the inflamed ST, and suggest that this resistance may be attributable to impaired IL-10-dependent STAT3 activation, in association with sustained STAT3 phosphorylation and SOCS1 induction."}
2_test
{"project":"2_test","denotations":[{"id":"15535835-11244051-4156906","span":{"begin":139,"end":140},"obj":"11244051"},{"id":"15535835-10898505-4156907","span":{"begin":315,"end":317},"obj":"10898505"}],"text":"IL-10 plays a predominant role in limiting immune and inflammatory responses by regulating the function of both macrophages and Th1 cells [1]. IL-10 inhibits the tyrosine phosphorylation of the CD28 molecule and the subsequent phosphatidylinositol 3-kinase binding in T cells, and thereby directly acts on T cells [24]. In the present study, we found that PB CD4+ T cells from patients with active RA, in the presence of IL-10, are able to produce higher levels of IFN-γ after CD3 and CD28 costimulation than normal CD4+ T cells. Despite high-level IL-10R1 expression and constitutive STAT3 activation, IL-10-induced tyrosine phosphorylation of STAT3 is suppressed in RA CD4+ T cells, in contrast to normal CD4+ T cells, where STAT3 phosphorylation is dose-dependently inducible by IL-10. Serum IL-6 from RA patients induces STAT3 but not STAT1 phosphorylation in normal CD4+ T cells, and exogenous IL-6 induces the resistance to IL-10 inhibition of IFN-γ production. RA CD4+ T cells contain higher levels of SOCS1 but contain lower levels of SOCS3 transcripts in comparison with normal CD4+ T cells. These findings indicate that CD4+ T cells become resistant to the inhibitory effect of IL-10 before migration into the inflamed ST, and suggest that this resistance may be attributable to impaired IL-10-dependent STAT3 activation, in association with sustained STAT3 phosphorylation and SOCS1 induction."}
pmc-enju-pas
{"project":"pmc-enju-pas","denotations":[{"id":"T24856","span":{"begin":1394,"end":1403},"obj":"NN"},{"id":"T24855","span":{"begin":1388,"end":1393},"obj":"NN"},{"id":"T24854","span":{"begin":1384,"end":1387},"obj":"CC"},{"id":"T24853","span":{"begin":1368,"end":1383},"obj":"NN"},{"id":"T24852","span":{"begin":1362,"end":1367},"obj":"NN"},{"id":"T24851","span":{"begin":1352,"end":1361},"obj":"JJ"},{"id":"T24850","span":{"begin":1347,"end":1351},"obj":"IN"},{"id":"T24849","span":{"begin":1335,"end":1346},"obj":"NN"},{"id":"T24848","span":{"begin":1332,"end":1334},"obj":"IN"},{"id":"T24847","span":{"begin":1330,"end":1331},"obj":"-COMMA-"},{"id":"T24846","span":{"begin":1320,"end":1330},"obj":"NN"},{"id":"T24845","span":{"begin":1314,"end":1319},"obj":"NN"},{"id":"T24844","span":{"begin":1298,"end":1313},"obj":"JJ"},{"id":"T24843","span":{"begin":1289,"end":1297},"obj":"JJ"},{"id":"T24842","span":{"begin":1286,"end":1288},"obj":"TO"},{"id":"T24841","span":{"begin":1273,"end":1285},"obj":"JJ"},{"id":"T24840","span":{"begin":1270,"end":1272},"obj":"VB"},{"id":"T24839","span":{"begin":1266,"end":1269},"obj":"MD"},{"id":"T24838","span":{"begin":1255,"end":1265},"obj":"NN"},{"id":"T24837","span":{"begin":1250,"end":1254},"obj":"DT"},{"id":"T24836","span":{"begin":1245,"end":1249},"obj":"IN"},{"id":"T24835","span":{"begin":1237,"end":1244},"obj":"VB"},{"id":"T24834","span":{"begin":1233,"end":1236},"obj":"CC"},{"id":"T24833","span":{"begin":1231,"end":1232},"obj":"-COMMA-"},{"id":"T24832","span":{"begin":1229,"end":1231},"obj":"NN"},{"id":"T24831","span":{"begin":1220,"end":1228},"obj":"JJ"},{"id":"T24830","span":{"begin":1216,"end":1219},"obj":"DT"},{"id":"T24829","span":{"begin":1211,"end":1215},"obj":"IN"},{"id":"T24828","span":{"begin":1201,"end":1210},"obj":"NN"},{"id":"T24827","span":{"begin":1194,"end":1200},"obj":"IN"},{"id":"T24826","span":{"begin":1188,"end":1193},"obj":"NN"},{"id":"T24825","span":{"begin":1185,"end":1187},"obj":"IN"},{"id":"T24824","span":{"begin":1178,"end":1184},"obj":"NN"},{"id":"T24823","span":{"begin":1167,"end":1177},"obj":"JJ"},{"id":"T24822","span":{"begin":1163,"end":1166},"obj":"DT"},{"id":"T24821","span":{"begin":1160,"end":1162},"obj":"TO"},{"id":"T24820","span":{"begin":1150,"end":1159},"obj":"JJ"},{"id":"T24819","span":{"begin":1143,"end":1149},"obj":"VB"},{"id":"T24818","span":{"begin":1137,"end":1142},"obj":"NN"},{"id":"T24817","span":{"begin":1135,"end":1136},"obj":"NN"},{"id":"T24816","span":{"begin":1130,"end":1134},"obj":"JJ"},{"id":"T24815","span":{"begin":1125,"end":1129},"obj":"IN"},{"id":"T24814","span":{"begin":1116,"end":1124},"obj":"VB"},{"id":"T24813","span":{"begin":1107,"end":1115},"obj":"NN"},{"id":"T24812","span":{"begin":1101,"end":1106},"obj":"DT"},{"id":"T24811","span":{"begin":1094,"end":1099},"obj":"NN"},{"id":"T24810","span":{"begin":1092,"end":1093},"obj":"NN"},{"id":"T24809","span":{"begin":1087,"end":1091},"obj":"JJ"},{"id":"T24808","span":{"begin":1080,"end":1086},"obj":"JJ"},{"id":"T24807","span":{"begin":1075,"end":1079},"obj":"IN"},{"id":"T24806","span":{"begin":1064,"end":1074},"obj":"NN"},{"id":"T24805","span":{"begin":1061,"end":1063},"obj":"IN"},{"id":"T24804","span":{"begin":1049,"end":1060},"obj":"NN"},{"id":"T24803","span":{"begin":1043,"end":1048},"obj":"NN"},{"id":"T24802","span":{"begin":1040,"end":1042},"obj":"IN"},{"id":"T24801","span":{"begin":1033,"end":1039},"obj":"NN"},{"id":"T24800","span":{"begin":1027,"end":1032},"obj":"JJ"},{"id":"T24799","span":{"begin":1019,"end":1026},"obj":"VB"},{"id":"T24798","span":{"begin":1015,"end":1018},"obj":"CC"},{"id":"T24797","span":{"begin":1009,"end":1014},"obj":"NN"},{"id":"T24796","span":{"begin":1006,"end":1008},"obj":"IN"},{"id":"T24795","span":{"begin":999,"end":1005},"obj":"NN"},{"id":"T24794","span":{"begin":992,"end":998},"obj":"JJ"},{"id":"T24793","span":{"begin":984,"end":991},"obj":"VB"},{"id":"T24792","span":{"begin":978,"end":983},"obj":"NN"},{"id":"T24791","span":{"begin":976,"end":977},"obj":"NN"},{"id":"T24790","span":{"begin":971,"end":975},"obj":"JJ"},{"id":"T24789","span":{"begin":968,"end":970},"obj":"NN"},{"id":"T24788","span":{"begin":956,"end":966},"obj":"NN"},{"id":"T24787","span":{"begin":950,"end":955},"obj":"NN"},{"id":"T24786","span":{"begin":947,"end":949},"obj":"IN"},{"id":"T24785","span":{"begin":936,"end":946},"obj":"NN"},{"id":"T24784","span":{"begin":930,"end":935},"obj":"NN"},{"id":"T24783","span":{"begin":927,"end":929},"obj":"TO"},{"id":"T24782","span":{"begin":916,"end":926},"obj":"NN"},{"id":"T24781","span":{"begin":912,"end":915},"obj":"DT"},{"id":"T24780","span":{"begin":904,"end":911},"obj":"VB"},{"id":"T24779","span":{"begin":899,"end":903},"obj":"NN"},{"id":"T24778","span":{"begin":889,"end":898},"obj":"JJ"},{"id":"T24777","span":{"begin":885,"end":888},"obj":"CC"},{"id":"T24776","span":{"begin":883,"end":884},"obj":"-COMMA-"},{"id":"T24775","span":{"begin":878,"end":883},"obj":"NN"},{"id":"T24774","span":{"begin":876,"end":877},"obj":"NN"},{"id":"T24773","span":{"begin":871,"end":875},"obj":"JJ"},{"id":"T24772","span":{"begin":864,"end":870},"obj":"JJ"},{"id":"T24771","span":{"begin":861,"end":863},"obj":"IN"},{"id":"T24770","span":{"begin":845,"end":860},"obj":"NN"},{"id":"T24769","span":{"begin":839,"end":844},"obj":"NN"},{"id":"T24768","span":{"begin":835,"end":838},"obj":"RB"},{"id":"T24767","span":{"begin":831,"end":834},"obj":"CC"},{"id":"T24766","span":{"begin":825,"end":830},"obj":"NN"},{"id":"T24765","span":{"begin":817,"end":824},"obj":"VB"},{"id":"T24764","span":{"begin":808,"end":816},"obj":"NN"},{"id":"T24763","span":{"begin":805,"end":807},"obj":"NN"},{"id":"T24762","span":{"begin":800,"end":804},"obj":"IN"},{"id":"T24761","span":{"begin":795,"end":799},"obj":"NN"},{"id":"T24760","span":{"begin":789,"end":794},"obj":"NN"},{"id":"T24759","span":{"begin":782,"end":787},"obj":"NN"},{"id":"T24758","span":{"begin":779,"end":781},"obj":"IN"},{"id":"T24757","span":{"begin":769,"end":778},"obj":"JJ"},{"id":"T24756","span":{"begin":752,"end":768},"obj":"RB"},{"id":"T24755","span":{"begin":749,"end":751},"obj":"VB"},{"id":"T24754","span":{"begin":733,"end":748},"obj":"NN"},{"id":"T24753","span":{"begin":727,"end":732},"obj":"NN"},{"id":"T24752","span":{"begin":721,"end":726},"obj":"WRB"},{"id":"T24751","span":{"begin":719,"end":720},"obj":"-COMMA-"},{"id":"T24750","span":{"begin":714,"end":719},"obj":"NN"},{"id":"T24749","span":{"begin":712,"end":713},"obj":"NN"},{"id":"T24748","span":{"begin":707,"end":711},"obj":"JJ"},{"id":"T24747","span":{"begin":700,"end":706},"obj":"JJ"},{"id":"T24746","span":{"begin":697,"end":699},"obj":"TO"},{"id":"T24745","span":{"begin":688,"end":696},"obj":"NN"},{"id":"T24744","span":{"begin":685,"end":687},"obj":"IN"},{"id":"T24743","span":{"begin":683,"end":684},"obj":"-COMMA-"},{"id":"T24742","span":{"begin":678,"end":683},"obj":"NN"},{"id":"T24741","span":{"begin":676,"end":677},"obj":"NN"},{"id":"T24740","span":{"begin":671,"end":675},"obj":"JJ"},{"id":"T24739","span":{"begin":668,"end":670},"obj":"NN"},{"id":"T24738","span":{"begin":665,"end":667},"obj":"IN"},{"id":"T24737","span":{"begin":654,"end":664},"obj":"VB"},{"id":"T24736","span":{"begin":651,"end":653},"obj":"VB"},{"id":"T24735","span":{"begin":645,"end":650},"obj":"NN"},{"id":"T24734","span":{"begin":642,"end":644},"obj":"IN"},{"id":"T24733","span":{"begin":626,"end":641},"obj":"NN"},{"id":"T24732","span":{"begin":617,"end":625},"obj":"NN"},{"id":"T24731","span":{"begin":603,"end":616},"obj":"JJ"},{"id":"T24730","span":{"begin":601,"end":602},"obj":"-COMMA-"},{"id":"T24729","span":{"begin":591,"end":601},"obj":"NN"},{"id":"T24728","span":{"begin":585,"end":590},"obj":"NN"},{"id":"T24727","span":{"begin":572,"end":584},"obj":"JJ"},{"id":"T24726","span":{"begin":568,"end":571},"obj":"CC"},{"id":"T24725","span":{"begin":557,"end":567},"obj":"NN"},{"id":"T24724","span":{"begin":549,"end":556},"obj":"NN"},{"id":"T24723","span":{"begin":538,"end":548},"obj":"JJ"},{"id":"T24722","span":{"begin":530,"end":537},"obj":"IN"},{"id":"T24721","span":{"begin":523,"end":528},"obj":"NN"},{"id":"T24720","span":{"begin":521,"end":522},"obj":"NN"},{"id":"T24719","span":{"begin":516,"end":520},"obj":"JJ"},{"id":"T24718","span":{"begin":509,"end":515},"obj":"JJ"},{"id":"T24717","span":{"begin":504,"end":508},"obj":"IN"},{"id":"T24716","span":{"begin":490,"end":503},"obj":"NN"},{"id":"T24715","span":{"begin":485,"end":489},"obj":"NN"},{"id":"T24714","span":{"begin":481,"end":484},"obj":"CC"},{"id":"T24713","span":{"begin":477,"end":480},"obj":"NN"},{"id":"T24712","span":{"begin":471,"end":476},"obj":"IN"},{"id":"T24711","span":{"begin":465,"end":470},"obj":"NN"},{"id":"T24710","span":{"begin":462,"end":464},"obj":"IN"},{"id":"T24709","span":{"begin":455,"end":461},"obj":"NN"},{"id":"T24708","span":{"begin":448,"end":454},"obj":"JJ"},{"id":"T24707","span":{"begin":440,"end":447},"obj":"VB"},{"id":"T24706","span":{"begin":437,"end":439},"obj":"TO"},{"id":"T24705","span":{"begin":432,"end":436},"obj":"JJ"},{"id":"T24704","span":{"begin":428,"end":431},"obj":"VB"},{"id":"T24703","span":{"begin":426,"end":427},"obj":"-COMMA-"},{"id":"T24702","span":{"begin":421,"end":426},"obj":"NN"},{"id":"T24670","span":{"begin":277,"end":280},"obj":"CC"},{"id":"T24669","span":{"begin":275,"end":276},"obj":"-COMMA-"},{"id":"T24668","span":{"begin":270,"end":275},"obj":"NN"},{"id":"T24667","span":{"begin":268,"end":269},"obj":"NN"},{"id":"T24666","span":{"begin":265,"end":267},"obj":"IN"},{"id":"T24665","span":{"begin":257,"end":264},"obj":"NN"},{"id":"T24664","span":{"begin":248,"end":256},"obj":"NN"},{"id":"T24663","span":{"begin":227,"end":247},"obj":"NN"},{"id":"T24662","span":{"begin":216,"end":226},"obj":"JJ"},{"id":"T24661","span":{"begin":212,"end":215},"obj":"DT"},{"id":"T24660","span":{"begin":208,"end":211},"obj":"CC"},{"id":"T24659","span":{"begin":199,"end":207},"obj":"NN"},{"id":"T24658","span":{"begin":194,"end":198},"obj":"NN"},{"id":"T24657","span":{"begin":190,"end":193},"obj":"DT"},{"id":"T24656","span":{"begin":187,"end":189},"obj":"IN"},{"id":"T24655","span":{"begin":171,"end":186},"obj":"NN"},{"id":"T24654","span":{"begin":162,"end":170},"obj":"NN"},{"id":"T24653","span":{"begin":158,"end":161},"obj":"DT"},{"id":"T24652","span":{"begin":149,"end":157},"obj":"VB"},{"id":"T24651","span":{"begin":143,"end":148},"obj":"NN"},{"id":"T24650","span":{"begin":140,"end":141},"obj":"-RRB-"},{"id":"T24649","span":{"begin":139,"end":140},"obj":"CD"},{"id":"T24648","span":{"begin":138,"end":139},"obj":"-LRB-"},{"id":"T24647","span":{"begin":132,"end":137},"obj":"NN"},{"id":"T24646","span":{"begin":128,"end":131},"obj":"NN"},{"id":"T24645","span":{"begin":124,"end":127},"obj":"CC"},{"id":"T24644","span":{"begin":112,"end":123},"obj":"NN"},{"id":"T24643","span":{"begin":107,"end":111},"obj":"CC"},{"id":"T24642","span":{"begin":104,"end":106},"obj":"IN"},{"id":"T24641","span":{"begin":95,"end":103},"obj":"NN"},{"id":"T24640","span":{"begin":91,"end":94},"obj":"DT"},{"id":"T24639","span":{"begin":80,"end":90},"obj":"VB"},{"id":"T24638","span":{"begin":77,"end":79},"obj":"IN"},{"id":"T24637","span":{"begin":67,"end":76},"obj":"NN"},{"id":"T24636","span":{"begin":54,"end":66},"obj":"JJ"},{"id":"T24635","span":{"begin":50,"end":53},"obj":"CC"},{"id":"T24634","span":{"begin":43,"end":49},"obj":"JJ"},{"id":"T24633","span":{"begin":34,"end":42},"obj":"VB"},{"id":"T24632","span":{"begin":31,"end":33},"obj":"IN"},{"id":"T24631","span":{"begin":26,"end":30},"obj":"NN"},{"id":"T24630","span":{"begin":14,"end":25},"obj":"JJ"},{"id":"T24629","span":{"begin":12,"end":13},"obj":"DT"},{"id":"T24628","span":{"begin":6,"end":11},"obj":"VB"},{"id":"T24627","span":{"begin":0,"end":5},"obj":"NN"},{"id":"T24701","span":{"begin":418,"end":420},"obj":"IN"},{"id":"T24700","span":{"begin":409,"end":417},"obj":"NN"},{"id":"T24699","span":{"begin":405,"end":408},"obj":"DT"},{"id":"T24698","span":{"begin":402,"end":404},"obj":"IN"},{"id":"T24697","span":{"begin":400,"end":401},"obj":"-COMMA-"},{"id":"T24696","span":{"begin":398,"end":400},"obj":"NN"},{"id":"T24695","span":{"begin":391,"end":397},"obj":"JJ"},{"id":"T24694","span":{"begin":386,"end":390},"obj":"IN"},{"id":"T24693","span":{"begin":377,"end":385},"obj":"NN"},{"id":"T24692","span":{"begin":372,"end":376},"obj":"IN"},{"id":"T24691","span":{"begin":366,"end":371},"obj":"NN"},{"id":"T24690","span":{"begin":364,"end":365},"obj":"NN"},{"id":"T24689","span":{"begin":359,"end":363},"obj":"JJ"},{"id":"T24688","span":{"begin":356,"end":358},"obj":"NN"},{"id":"T24687","span":{"begin":351,"end":355},"obj":"IN"},{"id":"T24686","span":{"begin":345,"end":350},"obj":"VB"},{"id":"T24685","span":{"begin":342,"end":344},"obj":"PRP"},{"id":"T24684","span":{"begin":340,"end":341},"obj":"-COMMA-"},{"id":"T24683","span":{"begin":335,"end":340},"obj":"NN"},{"id":"T24682","span":{"begin":327,"end":334},"obj":"JJ"},{"id":"T24681","span":{"begin":323,"end":326},"obj":"DT"},{"id":"T24680","span":{"begin":320,"end":322},"obj":"IN"},{"id":"T24679","span":{"begin":317,"end":318},"obj":"-RRB-"},{"id":"T24678","span":{"begin":315,"end":317},"obj":"CD"},{"id":"T24677","span":{"begin":314,"end":315},"obj":"-LRB-"},{"id":"T24676","span":{"begin":308,"end":313},"obj":"NN"},{"id":"T24675","span":{"begin":306,"end":307},"obj":"NN"},{"id":"T24674","span":{"begin":303,"end":305},"obj":"IN"},{"id":"T24673","span":{"begin":298,"end":302},"obj":"VB"},{"id":"T24672","span":{"begin":289,"end":297},"obj":"RB"},{"id":"T24671","span":{"begin":281,"end":288},"obj":"RB"}],"relations":[{"id":"R11682","pred":"arg1Of","subj":"T24627","obj":"T24628"},{"id":"R11683","pred":"arg1Of","subj":"T24627","obj":"T24633"},{"id":"R11684","pred":"arg1Of","subj":"T24627","obj":"T24639"},{"id":"R11685","pred":"arg1Of","subj":"T24628","obj":"T24632"},{"id":"R11686","pred":"arg2Of","subj":"T24631","obj":"T24628"},{"id":"R11687","pred":"arg1Of","subj":"T24631","obj":"T24629"},{"id":"R11688","pred":"arg1Of","subj":"T24631","obj":"T24630"},{"id":"R11689","pred":"arg2Of","subj":"T24633","obj":"T24632"},{"id":"R11690","pred":"arg1Of","subj":"T24633","obj":"T24638"},{"id":"R11691","pred":"arg1Of","subj":"T24634","obj":"T24635"},{"id":"R11692","pred":"arg2Of","subj":"T24636","obj":"T24635"},{"id":"R11693","pred":"arg2Of","subj":"T24637","obj":"T24633"},{"id":"R11694","pred":"arg1Of","subj":"T24637","obj":"T24634"},{"id":"R11695","pred":"arg1Of","subj":"T24637","obj":"T24636"},{"id":"R11696","pred":"arg2Of","subj":"T24639","obj":"T24638"},{"id":"R11697","pred":"arg2Of","subj":"T24641","obj":"T24639"},{"id":"R11698","pred":"arg1Of","subj":"T24641","obj":"T24640"},{"id":"R11699","pred":"arg1Of","subj":"T24641","obj":"T24642"},{"id":"R11700","pred":"arg1Of","subj":"T24644","obj":"T24645"},{"id":"R11701","pred":"arg2Of","subj":"T24645","obj":"T24642"},{"id":"R11702","pred":"arg1Of","subj":"T24645","obj":"T24643"},{"id":"R11703","pred":"arg1Of","subj":"T24645","obj":"T24648"},{"id":"R11704","pred":"arg2Of","subj":"T24647","obj":"T24645"},{"id":"R11705","pred":"arg1Of","subj":"T24647","obj":"T24646"},{"id":"R11706","pred":"arg2Of","subj":"T24649","obj":"T24648"},{"id":"R11707","pred":"arg3Of","subj":"T24650","obj":"T24648"},{"id":"R11708","pred":"arg1Of","subj":"T24651","obj":"T24652"},{"id":"R11709","pred":"arg1Of","subj":"T24651","obj":"T24673"},{"id":"R11710","pred":"arg1Of","subj":"T24652","obj":"T24670"},{"id":"R11711","pred":"arg1Of","subj":"T24655","obj":"T24653"},{"id":"R11712","pred":"arg1Of","subj":"T24655","obj":"T24654"},{"id":"R11713","pred":"arg1Of","subj":"T24655","obj":"T24656"},{"id":"R11714","pred":"arg1Of","subj":"T24655","obj":"T24660"},{"id":"R11715","pred":"arg2Of","subj":"T24659","obj":"T24656"},{"id":"R11716","pred":"arg1Of","subj":"T24659","obj":"T24657"},{"id":"R11717","pred":"arg1Of","subj":"T24659","obj":"T24658"},{"id":"R11718","pred":"arg2Of","subj":"T24660","obj":"T24652"},{"id":"R11719","pred":"arg2Of","subj":"T24665","obj":"T24660"},{"id":"R11720","pred":"arg1Of","subj":"T24665","obj":"T24661"},{"id":"R11721","pred":"arg1Of","subj":"T24665","obj":"T24662"},{"id":"R11722","pred":"arg1Of","subj":"T24665","obj":"T24663"},{"id":"R11723","pred":"arg1Of","subj":"T24665","obj":"T24664"},{"id":"R11724","pred":"arg1Of","subj":"T24665","obj":"T24666"},{"id":"R11725","pred":"arg2Of","subj":"T24668","obj":"T24666"},{"id":"R11726","pred":"arg1Of","subj":"T24668","obj":"T24667"},{"id":"R11727","pred":"arg1Of","subj":"T24670","obj":"T24669"},{"id":"R11728","pred":"arg2Of","subj":"T24673","obj":"T24670"},{"id":"R11729","pred":"arg1Of","subj":"T24673","obj":"T24671"},{"id":"R11730","pred":"arg1Of","subj":"T24673","obj":"T24672"},{"id":"R11731","pred":"arg1Of","subj":"T24673","obj":"T24674"},{"id":"R11732","pred":"arg1Of","subj":"T24673","obj":"T24677"},{"id":"R11733","pred":"arg2Of","subj":"T24676","obj":"T24674"},{"id":"R11734","pred":"arg1Of","subj":"T24676","obj":"T24675"},{"id":"R11735","pred":"arg2Of","subj":"T24678","obj":"T24677"},{"id":"R11736","pred":"arg3Of","subj":"T24679","obj":"T24677"},{"id":"R11737","pred":"arg2Of","subj":"T24683","obj":"T24680"},{"id":"R11738","pred":"arg1Of","subj":"T24683","obj":"T24681"},{"id":"R11739","pred":"arg1Of","subj":"T24683","obj":"T24682"},{"id":"R11740","pred":"arg1Of","subj":"T24685","obj":"T24686"},{"id":"R11741","pred":"arg1Of","subj":"T24686","obj":"T24680"},{"id":"R11742","pred":"arg1Of","subj":"T24686","obj":"T24684"},{"id":"R11743","pred":"arg1Of","subj":"T24691","obj":"T24688"},{"id":"R11744","pred":"arg1Of","subj":"T24691","obj":"T24689"},{"id":"R11745","pred":"arg1Of","subj":"T24691","obj":"T24690"},{"id":"R11746","pred":"arg1Of","subj":"T24691","obj":"T24692"},{"id":"R11747","pred":"arg1Of","subj":"T24691","obj":"T24704"},{"id":"R11748","pred":"arg1Of","subj":"T24691","obj":"T24705"},{"id":"R11749","pred":"arg1Of","subj":"T24691","obj":"T24707"},{"id":"R11750","pred":"arg2Of","subj":"T24693","obj":"T24692"},{"id":"R11751","pred":"arg1Of","subj":"T24693","obj":"T24694"},{"id":"R11752","pred":"arg2Of","subj":"T24696","obj":"T24694"},{"id":"R11753","pred":"arg1Of","subj":"T24696","obj":"T24695"},{"id":"R11754","pred":"arg2Of","subj":"T24700","obj":"T24698"},{"id":"R11755","pred":"arg1Of","subj":"T24700","obj":"T24699"},{"id":"R11756","pred":"arg1Of","subj":"T24700","obj":"T24701"},{"id":"R11757","pred":"arg2Of","subj":"T24702","obj":"T24701"},{"id":"R11758","pred":"arg2Of","subj":"T24704","obj":"T24686"},{"id":"R11759","pred":"arg1Of","subj":"T24704","obj":"T24687"},{"id":"R11760","pred":"arg1Of","subj":"T24704","obj":"T24697"},{"id":"R11761","pred":"arg1Of","subj":"T24704","obj":"T24698"},{"id":"R11762","pred":"arg1Of","subj":"T24704","obj":"T24703"},{"id":"R11763","pred":"arg2Of","subj":"T24705","obj":"T24704"},{"id":"R11764","pred":"arg2Of","subj":"T24707","obj":"T24705"},{"id":"R11765","pred":"arg1Of","subj":"T24707","obj":"T24706"},{"id":"R11766","pred":"arg2Of","subj":"T24709","obj":"T24707"},{"id":"R11767","pred":"arg1Of","subj":"T24709","obj":"T24708"},{"id":"R11768","pred":"arg1Of","subj":"T24709","obj":"T24710"},{"id":"R11769","pred":"arg2Of","subj":"T24711","obj":"T24710"},{"id":"R11770","pred":"arg1Of","subj":"T24711","obj":"T24712"},{"id":"R11771","pred":"arg1Of","subj":"T24711","obj":"T24717"},{"id":"R11772","pred":"arg1Of","subj":"T24713","obj":"T24714"},{"id":"R11773","pred":"arg2Of","subj":"T24715","obj":"T24714"},{"id":"R11774","pred":"arg2Of","subj":"T24716","obj":"T24712"},{"id":"R11775","pred":"arg1Of","subj":"T24716","obj":"T24713"},{"id":"R11776","pred":"arg1Of","subj":"T24716","obj":"T24715"},{"id":"R11777","pred":"arg2Of","subj":"T24721","obj":"T24717"},{"id":"R11778","pred":"arg1Of","subj":"T24721","obj":"T24718"},{"id":"R11779","pred":"arg1Of","subj":"T24721","obj":"T24719"},{"id":"R11780","pred":"arg1Of","subj":"T24721","obj":"T24720"},{"id":"R11781","pred":"arg1Of","subj":"T24725","obj":"T24723"},{"id":"R11782","pred":"arg1Of","subj":"T24725","obj":"T24724"},{"id":"R11783","pred":"arg1Of","subj":"T24725","obj":"T24726"},{"id":"R11784","pred":"arg2Of","subj":"T24726","obj":"T24722"},{"id":"R11785","pred":"arg2Of","subj":"T24729","obj":"T24726"},{"id":"R11786","pred":"arg1Of","subj":"T24729","obj":"T24727"},{"id":"R11787","pred":"arg1Of","subj":"T24729","obj":"T24728"},{"id":"R11788","pred":"arg1Of","subj":"T24733","obj":"T24731"},{"id":"R11789","pred":"arg1Of","subj":"T24733","obj":"T24732"},{"id":"R11790","pred":"arg1Of","subj":"T24733","obj":"T24734"},{"id":"R11791","pred":"arg1Of","subj":"T24733","obj":"T24736"},{"id":"R11792","pred":"arg2Of","subj":"T24733","obj":"T24737"},{"id":"R11793","pred":"arg2Of","subj":"T24735","obj":"T24734"},{"id":"R11794","pred":"arg1Of","subj":"T24737","obj":"T24722"},{"id":"R11795","pred":"arg1Of","subj":"T24737","obj":"T24730"},{"id":"R11796","pred":"arg2Of","subj":"T24737","obj":"T24736"},{"id":"R11797","pred":"arg1Of","subj":"T24737","obj":"T24738"},{"id":"R11798","pred":"arg1Of","subj":"T24737","obj":"T24743"},{"id":"R11799","pred":"arg1Of","subj":"T24737","obj":"T24744"},{"id":"R11800","pred":"arg2Of","subj":"T24742","obj":"T24738"},{"id":"R11801","pred":"arg1Of","subj":"T24742","obj":"T24739"},{"id":"R11802","pred":"arg1Of","subj":"T24742","obj":"T24740"},{"id":"R11803","pred":"arg1Of","subj":"T24742","obj":"T24741"},{"id":"R11804","pred":"arg2Of","subj":"T24745","obj":"T24744"},{"id":"R11805","pred":"arg1Of","subj":"T24745","obj":"T24746"},{"id":"R11806","pred":"arg2Of","subj":"T24750","obj":"T24746"},{"id":"R11807","pred":"arg1Of","subj":"T24750","obj":"T24747"},{"id":"R11808","pred":"arg1Of","subj":"T24750","obj":"T24748"},{"id":"R11809","pred":"arg1Of","subj":"T24750","obj":"T24749"},{"id":"R11810","pred":"arg1Of","subj":"T24750","obj":"T24751"},{"id":"R11811","pred":"arg1Of","subj":"T24750","obj":"T24752"},{"id":"R11812","pred":"arg1Of","subj":"T24754","obj":"T24753"},{"id":"R11813","pred":"arg1Of","subj":"T24754","obj":"T24755"},{"id":"R11814","pred":"arg1Of","subj":"T24754","obj":"T24757"},{"id":"R11815","pred":"arg2Of","subj":"T24755","obj":"T24752"},{"id":"R11816","pred":"arg2Of","subj":"T24757","obj":"T24755"},{"id":"R11817","pred":"arg1Of","subj":"T24757","obj":"T24756"},{"id":"R11818","pred":"arg1Of","subj":"T24757","obj":"T24758"},{"id":"R11819","pred":"arg2Of","subj":"T24759","obj":"T24758"},{"id":"R11820","pred":"arg1Of","subj":"T24761","obj":"T24760"},{"id":"R11821","pred":"arg1Of","subj":"T24761","obj":"T24762"},{"id":"R11822","pred":"arg1Of","subj":"T24761","obj":"T24765"},{"id":"R11823","pred":"arg2Of","subj":"T24764","obj":"T24762"},{"id":"R11824","pred":"arg1Of","subj":"T24764","obj":"T24763"},{"id":"R11825","pred":"arg1Of","subj":"T24765","obj":"T24771"},{"id":"R11826","pred":"arg1Of","subj":"T24765","obj":"T24777"},{"id":"R11827","pred":"arg1Of","subj":"T24766","obj":"T24767"},{"id":"R11828","pred":"arg2Of","subj":"T24767","obj":"T24765"},{"id":"R11829","pred":"arg1Of","subj":"T24767","obj":"T24768"},{"id":"R11830","pred":"arg2Of","subj":"T24770","obj":"T24767"},{"id":"R11831","pred":"arg1Of","subj":"T24770","obj":"T24769"},{"id":"R11832","pred":"arg2Of","subj":"T24775","obj":"T24771"},{"id":"R11833","pred":"arg1Of","subj":"T24775","obj":"T24772"},{"id":"R11834","pred":"arg1Of","subj":"T24775","obj":"T24773"},{"id":"R11835","pred":"arg1Of","subj":"T24775","obj":"T24774"},{"id":"R11836","pred":"arg1Of","subj":"T24777","obj":"T24776"},{"id":"R11837","pred":"arg1Of","subj":"T24779","obj":"T24778"},{"id":"R11838","pred":"arg1Of","subj":"T24779","obj":"T24780"},{"id":"R11839","pred":"arg2Of","subj":"T24780","obj":"T24777"},{"id":"R11840","pred":"arg2Of","subj":"T24782","obj":"T24780"},{"id":"R11841","pred":"arg1Of","subj":"T24782","obj":"T24781"},{"id":"R11842","pred":"arg1Of","subj":"T24782","obj":"T24783"},{"id":"R11843","pred":"arg2Of","subj":"T24785","obj":"T24783"},{"id":"R11844","pred":"arg1Of","subj":"T24785","obj":"T24784"},{"id":"R11845","pred":"arg1Of","subj":"T24785","obj":"T24786"},{"id":"R11846","pred":"arg2Of","subj":"T24788","obj":"T24786"},{"id":"R11847","pred":"arg1Of","subj":"T24788","obj":"T24787"},{"id":"R11848","pred":"arg1Of","subj":"T24792","obj":"T24789"},{"id":"R11849","pred":"arg1Of","subj":"T24792","obj":"T24790"},{"id":"R11850","pred":"arg1Of","subj":"T24792","obj":"T24791"},{"id":"R11851","pred":"arg1Of","subj":"T24792","obj":"T24793"},{"id":"R11852","pred":"arg1Of","subj":"T24792","obj":"T24799"},{"id":"R11853","pred":"arg1Of","subj":"T24793","obj":"T24798"},{"id":"R11854","pred":"arg2Of","subj":"T24795","obj":"T24793"},{"id":"R11855","pred":"arg1Of","subj":"T24795","obj":"T24794"},{"id":"R11856","pred":"arg1Of","subj":"T24795","obj":"T24796"},{"id":"R11857","pred":"arg2Of","subj":"T24797","obj":"T24796"},{"id":"R11858","pred":"arg2Of","subj":"T24799","obj":"T24798"},{"id":"R11859","pred":"arg1Of","subj":"T24799","obj":"T24805"},{"id":"R11860","pred":"arg2Of","subj":"T24801","obj":"T24799"},{"id":"R11861","pred":"arg1Of","subj":"T24801","obj":"T24800"},{"id":"R11862","pred":"arg1Of","subj":"T24801","obj":"T24802"},{"id":"R11863","pred":"arg2Of","subj":"T24804","obj":"T24802"},{"id":"R11864","pred":"arg1Of","subj":"T24804","obj":"T24803"},{"id":"R11865","pred":"arg2Of","subj":"T24806","obj":"T24805"},{"id":"R11866","pred":"arg1Of","subj":"T24806","obj":"T24807"},{"id":"R11867","pred":"arg2Of","subj":"T24811","obj":"T24807"},{"id":"R11868","pred":"arg1Of","subj":"T24811","obj":"T24808"},{"id":"R11869","pred":"arg1Of","subj":"T24811","obj":"T24809"},{"id":"R11870","pred":"arg1Of","subj":"T24811","obj":"T24810"},{"id":"R11871","pred":"arg1Of","subj":"T24813","obj":"T24812"},{"id":"R11872","pred":"arg1Of","subj":"T24813","obj":"T24814"},{"id":"R11873","pred":"arg1Of","subj":"T24818","obj":"T24816"},{"id":"R11874","pred":"arg1Of","subj":"T24818","obj":"T24817"},{"id":"R11875","pred":"arg1Of","subj":"T24818","obj":"T24819"},{"id":"R11876","pred":"arg1Of","subj":"T24818","obj":"T24820"},{"id":"R11877","pred":"arg1Of","subj":"T24818","obj":"T24835"},{"id":"R11878","pred":"arg1Of","subj":"T24819","obj":"T24834"},{"id":"R11879","pred":"arg2Of","subj":"T24820","obj":"T24819"},{"id":"R11880","pred":"arg1Of","subj":"T24820","obj":"T24821"},{"id":"R11881","pred":"arg2Of","subj":"T24824","obj":"T24821"},{"id":"R11882","pred":"arg1Of","subj":"T24824","obj":"T24822"},{"id":"R11883","pred":"arg1Of","subj":"T24824","obj":"T24823"},{"id":"R11884","pred":"arg1Of","subj":"T24824","obj":"T24825"},{"id":"R11885","pred":"arg1Of","subj":"T24824","obj":"T24827"},{"id":"R11886","pred":"arg1Of","subj":"T24824","obj":"T24829"},{"id":"R11887","pred":"arg2Of","subj":"T24826","obj":"T24825"},{"id":"R11888","pred":"arg2Of","subj":"T24828","obj":"T24827"},{"id":"R11889","pred":"arg2Of","subj":"T24832","obj":"T24829"},{"id":"R11890","pred":"arg1Of","subj":"T24832","obj":"T24830"},{"id":"R11891","pred":"arg1Of","subj":"T24832","obj":"T24831"},{"id":"R11892","pred":"arg2Of","subj":"T24834","obj":"T24814"},{"id":"R11893","pred":"arg1Of","subj":"T24834","obj":"T24815"},{"id":"R11894","pred":"arg1Of","subj":"T24834","obj":"T24833"},{"id":"R11895","pred":"arg2Of","subj":"T24835","obj":"T24834"},{"id":"R11896","pred":"arg1Of","subj":"T24838","obj":"T24837"},{"id":"R11897","pred":"arg1Of","subj":"T24838","obj":"T24839"},{"id":"R11898","pred":"arg1Of","subj":"T24838","obj":"T24840"},{"id":"R11899","pred":"arg1Of","subj":"T24838","obj":"T24841"},{"id":"R11900","pred":"arg2Of","subj":"T24840","obj":"T24835"},{"id":"R11901","pred":"arg1Of","subj":"T24840","obj":"T24836"},{"id":"R11902","pred":"arg2Of","subj":"T24840","obj":"T24839"},{"id":"R11903","pred":"arg1Of","subj":"T24840","obj":"T24847"},{"id":"R11904","pred":"arg1Of","subj":"T24840","obj":"T24848"},{"id":"R11905","pred":"arg2Of","subj":"T24841","obj":"T24840"},{"id":"R11906","pred":"arg1Of","subj":"T24841","obj":"T24842"},{"id":"R11907","pred":"arg1Of","subj":"T24844","obj":"T24843"},{"id":"R11908","pred":"arg2Of","subj":"T24846","obj":"T24842"},{"id":"R11909","pred":"arg1Of","subj":"T24846","obj":"T24844"},{"id":"R11910","pred":"arg1Of","subj":"T24846","obj":"T24845"},{"id":"R11911","pred":"arg2Of","subj":"T24849","obj":"T24848"},{"id":"R11912","pred":"arg1Of","subj":"T24849","obj":"T24850"},{"id":"R11913","pred":"arg1Of","subj":"T24853","obj":"T24851"},{"id":"R11914","pred":"arg1Of","subj":"T24853","obj":"T24852"},{"id":"R11915","pred":"arg1Of","subj":"T24853","obj":"T24854"},{"id":"R11916","pred":"arg2Of","subj":"T24854","obj":"T24850"},{"id":"R11917","pred":"arg2Of","subj":"T24856","obj":"T24854"},{"id":"R11918","pred":"arg1Of","subj":"T24856","obj":"T24855"}],"namespaces":[{"prefix":"_base","uri":"http://kmcs.nii.ac.jp/enju/"}],"text":"IL-10 plays a predominant role in limiting immune and inflammatory responses by regulating the function of both macrophages and Th1 cells [1]. IL-10 inhibits the tyrosine phosphorylation of the CD28 molecule and the subsequent phosphatidylinositol 3-kinase binding in T cells, and thereby directly acts on T cells [24]. In the present study, we found that PB CD4+ T cells from patients with active RA, in the presence of IL-10, are able to produce higher levels of IFN-γ after CD3 and CD28 costimulation than normal CD4+ T cells. Despite high-level IL-10R1 expression and constitutive STAT3 activation, IL-10-induced tyrosine phosphorylation of STAT3 is suppressed in RA CD4+ T cells, in contrast to normal CD4+ T cells, where STAT3 phosphorylation is dose-dependently inducible by IL-10. Serum IL-6 from RA patients induces STAT3 but not STAT1 phosphorylation in normal CD4+ T cells, and exogenous IL-6 induces the resistance to IL-10 inhibition of IFN-γ production. RA CD4+ T cells contain higher levels of SOCS1 but contain lower levels of SOCS3 transcripts in comparison with normal CD4+ T cells. These findings indicate that CD4+ T cells become resistant to the inhibitory effect of IL-10 before migration into the inflamed ST, and suggest that this resistance may be attributable to impaired IL-10-dependent STAT3 activation, in association with sustained STAT3 phosphorylation and SOCS1 induction."}
bionlp-st-ge-2016-test-proteins
{"project":"bionlp-st-ge-2016-test-proteins","denotations":[{"id":"T23380","span":{"begin":1388,"end":1393},"obj":"Protein"},{"id":"T23379","span":{"begin":1362,"end":1367},"obj":"Protein"},{"id":"T23378","span":{"begin":1314,"end":1319},"obj":"Protein"},{"id":"T23377","span":{"begin":1298,"end":1303},"obj":"Protein"},{"id":"T23376","span":{"begin":1188,"end":1193},"obj":"Protein"},{"id":"T23375","span":{"begin":1130,"end":1133},"obj":"Protein"},{"id":"T23374","span":{"begin":1087,"end":1090},"obj":"Protein"},{"id":"T23373","span":{"begin":1043,"end":1048},"obj":"Protein"},{"id":"T23372","span":{"begin":1009,"end":1014},"obj":"Protein"},{"id":"T23371","span":{"begin":971,"end":974},"obj":"Protein"},{"id":"T23370","span":{"begin":950,"end":955},"obj":"Protein"},{"id":"T23369","span":{"begin":930,"end":935},"obj":"Protein"},{"id":"T23368","span":{"begin":899,"end":903},"obj":"Protein"},{"id":"T23367","span":{"begin":871,"end":874},"obj":"Protein"},{"id":"T23366","span":{"begin":839,"end":844},"obj":"Protein"},{"id":"T23365","span":{"begin":825,"end":830},"obj":"Protein"},{"id":"T23364","span":{"begin":795,"end":799},"obj":"Protein"},{"id":"T23363","span":{"begin":782,"end":787},"obj":"Protein"},{"id":"T23362","span":{"begin":727,"end":732},"obj":"Protein"},{"id":"T23361","span":{"begin":707,"end":710},"obj":"Protein"},{"id":"T23360","span":{"begin":671,"end":674},"obj":"Protein"},{"id":"T23359","span":{"begin":645,"end":650},"obj":"Protein"},{"id":"T23358","span":{"begin":603,"end":608},"obj":"Protein"},{"id":"T23357","span":{"begin":585,"end":590},"obj":"Protein"},{"id":"T23356","span":{"begin":549,"end":556},"obj":"Protein"},{"id":"T23355","span":{"begin":516,"end":519},"obj":"Protein"},{"id":"T23354","span":{"begin":485,"end":489},"obj":"Protein"},{"id":"T23353","span":{"begin":465,"end":470},"obj":"Protein"},{"id":"T23352","span":{"begin":421,"end":426},"obj":"Protein"},{"id":"T23351","span":{"begin":359,"end":362},"obj":"Protein"},{"id":"T23350","span":{"begin":194,"end":198},"obj":"Protein"},{"id":"T23349","span":{"begin":143,"end":148},"obj":"Protein"},{"id":"T23348","span":{"begin":0,"end":5},"obj":"Protein"}],"namespaces":[{"prefix":"_base","uri":"http://bionlp.dbcls.jp/ontology/ge.owl#"}],"text":"IL-10 plays a predominant role in limiting immune and inflammatory responses by regulating the function of both macrophages and Th1 cells [1]. IL-10 inhibits the tyrosine phosphorylation of the CD28 molecule and the subsequent phosphatidylinositol 3-kinase binding in T cells, and thereby directly acts on T cells [24]. In the present study, we found that PB CD4+ T cells from patients with active RA, in the presence of IL-10, are able to produce higher levels of IFN-γ after CD3 and CD28 costimulation than normal CD4+ T cells. Despite high-level IL-10R1 expression and constitutive STAT3 activation, IL-10-induced tyrosine phosphorylation of STAT3 is suppressed in RA CD4+ T cells, in contrast to normal CD4+ T cells, where STAT3 phosphorylation is dose-dependently inducible by IL-10. Serum IL-6 from RA patients induces STAT3 but not STAT1 phosphorylation in normal CD4+ T cells, and exogenous IL-6 induces the resistance to IL-10 inhibition of IFN-γ production. RA CD4+ T cells contain higher levels of SOCS1 but contain lower levels of SOCS3 transcripts in comparison with normal CD4+ T cells. These findings indicate that CD4+ T cells become resistant to the inhibitory effect of IL-10 before migration into the inflamed ST, and suggest that this resistance may be attributable to impaired IL-10-dependent STAT3 activation, in association with sustained STAT3 phosphorylation and SOCS1 induction."}
bionlp-st-ge-2016-uniprot
{"project":"bionlp-st-ge-2016-uniprot","denotations":[{"id":"T26419","span":{"begin":899,"end":903},"obj":"http://www.uniprot.org/uniprot/P05231"},{"id":"T26418","span":{"begin":795,"end":799},"obj":"http://www.uniprot.org/uniprot/P05231"},{"id":"T26395","span":{"begin":1362,"end":1367},"obj":"http://www.uniprot.org/uniprot/P40763"},{"id":"T26394","span":{"begin":1314,"end":1319},"obj":"http://www.uniprot.org/uniprot/P40763"},{"id":"T26393","span":{"begin":825,"end":830},"obj":"http://www.uniprot.org/uniprot/P40763"},{"id":"T26392","span":{"begin":727,"end":732},"obj":"http://www.uniprot.org/uniprot/P40763"},{"id":"T26391","span":{"begin":645,"end":650},"obj":"http://www.uniprot.org/uniprot/P40763"},{"id":"T26390","span":{"begin":585,"end":590},"obj":"http://www.uniprot.org/uniprot/P40763"},{"id":"T26389","span":{"begin":477,"end":480},"obj":"http://www.uniprot.org/uniprot/P09693"},{"id":"T26388","span":{"begin":477,"end":480},"obj":"http://www.uniprot.org/uniprot/P07766"},{"id":"T26387","span":{"begin":477,"end":480},"obj":"http://www.uniprot.org/uniprot/P04234"},{"id":"T26386","span":{"begin":477,"end":480},"obj":"http://www.uniprot.org/uniprot/P20963"},{"id":"T26377","span":{"begin":950,"end":955},"obj":"http://www.uniprot.org/uniprot/P01579"},{"id":"T26376","span":{"begin":465,"end":470},"obj":"http://www.uniprot.org/uniprot/P01579"},{"id":"T24280","span":{"begin":1298,"end":1303},"obj":"http://www.uniprot.org/uniprot/P22301"},{"id":"T24279","span":{"begin":1188,"end":1193},"obj":"http://www.uniprot.org/uniprot/P22301"},{"id":"T24278","span":{"begin":930,"end":935},"obj":"http://www.uniprot.org/uniprot/P22301"},{"id":"T24277","span":{"begin":782,"end":787},"obj":"http://www.uniprot.org/uniprot/P22301"},{"id":"T24276","span":{"begin":603,"end":608},"obj":"http://www.uniprot.org/uniprot/P22301"},{"id":"T24275","span":{"begin":421,"end":426},"obj":"http://www.uniprot.org/uniprot/P22301"},{"id":"T24274","span":{"begin":143,"end":148},"obj":"http://www.uniprot.org/uniprot/P22301"},{"id":"T24273","span":{"begin":0,"end":5},"obj":"http://www.uniprot.org/uniprot/P22301"},{"id":"T24266","span":{"begin":485,"end":489},"obj":"http://www.uniprot.org/uniprot/P10747"},{"id":"T24265","span":{"begin":194,"end":198},"obj":"http://www.uniprot.org/uniprot/P10747"},{"id":"T24240","span":{"begin":971,"end":974},"obj":"http://www.uniprot.org/uniprot/P01730"},{"id":"T24239","span":{"begin":871,"end":874},"obj":"http://www.uniprot.org/uniprot/P01730"},{"id":"T24238","span":{"begin":707,"end":710},"obj":"http://www.uniprot.org/uniprot/P01730"},{"id":"T24237","span":{"begin":671,"end":674},"obj":"http://www.uniprot.org/uniprot/P01730"},{"id":"T24236","span":{"begin":516,"end":519},"obj":"http://www.uniprot.org/uniprot/P01730"},{"id":"T24235","span":{"begin":359,"end":362},"obj":"http://www.uniprot.org/uniprot/P01730"},{"id":"T24242","span":{"begin":1130,"end":1133},"obj":"http://www.uniprot.org/uniprot/P01730"},{"id":"T24241","span":{"begin":1087,"end":1090},"obj":"http://www.uniprot.org/uniprot/P01730"},{"id":"T26439","span":{"begin":1388,"end":1393},"obj":"http://www.uniprot.org/uniprot/O15524"},{"id":"T26438","span":{"begin":1009,"end":1014},"obj":"http://www.uniprot.org/uniprot/O15524"}],"namespaces":[{"prefix":"_base","uri":"http://www.uniprot.org/uniprot/"}],"text":"IL-10 plays a predominant role in limiting immune and inflammatory responses by regulating the function of both macrophages and Th1 cells [1]. IL-10 inhibits the tyrosine phosphorylation of the CD28 molecule and the subsequent phosphatidylinositol 3-kinase binding in T cells, and thereby directly acts on T cells [24]. In the present study, we found that PB CD4+ T cells from patients with active RA, in the presence of IL-10, are able to produce higher levels of IFN-γ after CD3 and CD28 costimulation than normal CD4+ T cells. Despite high-level IL-10R1 expression and constitutive STAT3 activation, IL-10-induced tyrosine phosphorylation of STAT3 is suppressed in RA CD4+ T cells, in contrast to normal CD4+ T cells, where STAT3 phosphorylation is dose-dependently inducible by IL-10. Serum IL-6 from RA patients induces STAT3 but not STAT1 phosphorylation in normal CD4+ T cells, and exogenous IL-6 induces the resistance to IL-10 inhibition of IFN-γ production. RA CD4+ T cells contain higher levels of SOCS1 but contain lower levels of SOCS3 transcripts in comparison with normal CD4+ T cells. These findings indicate that CD4+ T cells become resistant to the inhibitory effect of IL-10 before migration into the inflamed ST, and suggest that this resistance may be attributable to impaired IL-10-dependent STAT3 activation, in association with sustained STAT3 phosphorylation and SOCS1 induction."}
GO-BP
{"project":"GO-BP","denotations":[{"id":"T22881","span":{"begin":936,"end":955},"obj":"http://purl.obolibrary.org/obo/GO_1902714"},{"id":"T22879","span":{"begin":1368,"end":1383},"obj":"http://purl.obolibrary.org/obo/GO_0016310"},{"id":"T22878","span":{"begin":845,"end":860},"obj":"http://purl.obolibrary.org/obo/GO_0016310"},{"id":"T22877","span":{"begin":733,"end":748},"obj":"http://purl.obolibrary.org/obo/GO_0016310"},{"id":"T22876","span":{"begin":626,"end":641},"obj":"http://purl.obolibrary.org/obo/GO_0016310"},{"id":"T22875","span":{"begin":171,"end":186},"obj":"http://purl.obolibrary.org/obo/GO_0016310"},{"id":"T22866","span":{"begin":54,"end":76},"obj":"http://purl.obolibrary.org/obo/GO_0006954"}],"text":"IL-10 plays a predominant role in limiting immune and inflammatory responses by regulating the function of both macrophages and Th1 cells [1]. IL-10 inhibits the tyrosine phosphorylation of the CD28 molecule and the subsequent phosphatidylinositol 3-kinase binding in T cells, and thereby directly acts on T cells [24]. In the present study, we found that PB CD4+ T cells from patients with active RA, in the presence of IL-10, are able to produce higher levels of IFN-γ after CD3 and CD28 costimulation than normal CD4+ T cells. Despite high-level IL-10R1 expression and constitutive STAT3 activation, IL-10-induced tyrosine phosphorylation of STAT3 is suppressed in RA CD4+ T cells, in contrast to normal CD4+ T cells, where STAT3 phosphorylation is dose-dependently inducible by IL-10. Serum IL-6 from RA patients induces STAT3 but not STAT1 phosphorylation in normal CD4+ T cells, and exogenous IL-6 induces the resistance to IL-10 inhibition of IFN-γ production. RA CD4+ T cells contain higher levels of SOCS1 but contain lower levels of SOCS3 transcripts in comparison with normal CD4+ T cells. These findings indicate that CD4+ T cells become resistant to the inhibitory effect of IL-10 before migration into the inflamed ST, and suggest that this resistance may be attributable to impaired IL-10-dependent STAT3 activation, in association with sustained STAT3 phosphorylation and SOCS1 induction."}
GO-CC
{"project":"GO-CC","denotations":[{"id":"T23662","span":{"begin":1137,"end":1142},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T23661","span":{"begin":1094,"end":1099},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T23660","span":{"begin":978,"end":983},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T23659","span":{"begin":878,"end":883},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T23658","span":{"begin":714,"end":719},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T23657","span":{"begin":678,"end":683},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T23656","span":{"begin":523,"end":528},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T23655","span":{"begin":366,"end":371},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T23654","span":{"begin":308,"end":313},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T23653","span":{"begin":270,"end":275},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T23652","span":{"begin":132,"end":137},"obj":"http://purl.obolibrary.org/obo/GO_0005623"}],"text":"IL-10 plays a predominant role in limiting immune and inflammatory responses by regulating the function of both macrophages and Th1 cells [1]. IL-10 inhibits the tyrosine phosphorylation of the CD28 molecule and the subsequent phosphatidylinositol 3-kinase binding in T cells, and thereby directly acts on T cells [24]. In the present study, we found that PB CD4+ T cells from patients with active RA, in the presence of IL-10, are able to produce higher levels of IFN-γ after CD3 and CD28 costimulation than normal CD4+ T cells. Despite high-level IL-10R1 expression and constitutive STAT3 activation, IL-10-induced tyrosine phosphorylation of STAT3 is suppressed in RA CD4+ T cells, in contrast to normal CD4+ T cells, where STAT3 phosphorylation is dose-dependently inducible by IL-10. Serum IL-6 from RA patients induces STAT3 but not STAT1 phosphorylation in normal CD4+ T cells, and exogenous IL-6 induces the resistance to IL-10 inhibition of IFN-γ production. RA CD4+ T cells contain higher levels of SOCS1 but contain lower levels of SOCS3 transcripts in comparison with normal CD4+ T cells. These findings indicate that CD4+ T cells become resistant to the inhibitory effect of IL-10 before migration into the inflamed ST, and suggest that this resistance may be attributable to impaired IL-10-dependent STAT3 activation, in association with sustained STAT3 phosphorylation and SOCS1 induction."}
GO-MF
{"project":"GO-MF","denotations":[{"id":"T23601","span":{"begin":899,"end":903},"obj":"http://purl.obolibrary.org/obo/GO_0005138"},{"id":"T23600","span":{"begin":795,"end":799},"obj":"http://purl.obolibrary.org/obo/GO_0005138"},{"id":"T23599","span":{"begin":250,"end":264},"obj":"http://purl.obolibrary.org/obo/GO_0019900"},{"id":"T23596","span":{"begin":139,"end":145},"obj":"http://purl.obolibrary.org/obo/GO_0005149"},{"id":"T23561","span":{"begin":1298,"end":1303},"obj":"http://purl.obolibrary.org/obo/GO_0005141"},{"id":"T23560","span":{"begin":1188,"end":1193},"obj":"http://purl.obolibrary.org/obo/GO_0005141"},{"id":"T23559","span":{"begin":930,"end":935},"obj":"http://purl.obolibrary.org/obo/GO_0005141"},{"id":"T23558","span":{"begin":782,"end":787},"obj":"http://purl.obolibrary.org/obo/GO_0005141"},{"id":"T23557","span":{"begin":603,"end":608},"obj":"http://purl.obolibrary.org/obo/GO_0005141"},{"id":"T23556","span":{"begin":421,"end":426},"obj":"http://purl.obolibrary.org/obo/GO_0005141"},{"id":"T23555","span":{"begin":143,"end":148},"obj":"http://purl.obolibrary.org/obo/GO_0005141"},{"id":"T23554","span":{"begin":0,"end":5},"obj":"http://purl.obolibrary.org/obo/GO_0005141"},{"id":"T23548","span":{"begin":257,"end":264},"obj":"http://purl.obolibrary.org/obo/GO_0005488"}],"text":"IL-10 plays a predominant role in limiting immune and inflammatory responses by regulating the function of both macrophages and Th1 cells [1]. IL-10 inhibits the tyrosine phosphorylation of the CD28 molecule and the subsequent phosphatidylinositol 3-kinase binding in T cells, and thereby directly acts on T cells [24]. In the present study, we found that PB CD4+ T cells from patients with active RA, in the presence of IL-10, are able to produce higher levels of IFN-γ after CD3 and CD28 costimulation than normal CD4+ T cells. Despite high-level IL-10R1 expression and constitutive STAT3 activation, IL-10-induced tyrosine phosphorylation of STAT3 is suppressed in RA CD4+ T cells, in contrast to normal CD4+ T cells, where STAT3 phosphorylation is dose-dependently inducible by IL-10. Serum IL-6 from RA patients induces STAT3 but not STAT1 phosphorylation in normal CD4+ T cells, and exogenous IL-6 induces the resistance to IL-10 inhibition of IFN-γ production. RA CD4+ T cells contain higher levels of SOCS1 but contain lower levels of SOCS3 transcripts in comparison with normal CD4+ T cells. These findings indicate that CD4+ T cells become resistant to the inhibitory effect of IL-10 before migration into the inflamed ST, and suggest that this resistance may be attributable to impaired IL-10-dependent STAT3 activation, in association with sustained STAT3 phosphorylation and SOCS1 induction."}
sentences
{"project":"sentences","denotations":[{"id":"T22808","span":{"begin":1101,"end":1404},"obj":"Sentence"},{"id":"T22807","span":{"begin":968,"end":1100},"obj":"Sentence"},{"id":"T22806","span":{"begin":789,"end":967},"obj":"Sentence"},{"id":"T22805","span":{"begin":530,"end":788},"obj":"Sentence"},{"id":"T22804","span":{"begin":320,"end":529},"obj":"Sentence"},{"id":"T22803","span":{"begin":143,"end":319},"obj":"Sentence"},{"id":"T22802","span":{"begin":0,"end":142},"obj":"Sentence"},{"id":"T145","span":{"begin":0,"end":142},"obj":"Sentence"},{"id":"T146","span":{"begin":143,"end":319},"obj":"Sentence"},{"id":"T147","span":{"begin":320,"end":529},"obj":"Sentence"},{"id":"T148","span":{"begin":530,"end":788},"obj":"Sentence"},{"id":"T149","span":{"begin":789,"end":967},"obj":"Sentence"},{"id":"T150","span":{"begin":968,"end":1100},"obj":"Sentence"},{"id":"T151","span":{"begin":1101,"end":1404},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"IL-10 plays a predominant role in limiting immune and inflammatory responses by regulating the function of both macrophages and Th1 cells [1]. IL-10 inhibits the tyrosine phosphorylation of the CD28 molecule and the subsequent phosphatidylinositol 3-kinase binding in T cells, and thereby directly acts on T cells [24]. In the present study, we found that PB CD4+ T cells from patients with active RA, in the presence of IL-10, are able to produce higher levels of IFN-γ after CD3 and CD28 costimulation than normal CD4+ T cells. Despite high-level IL-10R1 expression and constitutive STAT3 activation, IL-10-induced tyrosine phosphorylation of STAT3 is suppressed in RA CD4+ T cells, in contrast to normal CD4+ T cells, where STAT3 phosphorylation is dose-dependently inducible by IL-10. Serum IL-6 from RA patients induces STAT3 but not STAT1 phosphorylation in normal CD4+ T cells, and exogenous IL-6 induces the resistance to IL-10 inhibition of IFN-γ production. RA CD4+ T cells contain higher levels of SOCS1 but contain lower levels of SOCS3 transcripts in comparison with normal CD4+ T cells. These findings indicate that CD4+ T cells become resistant to the inhibitory effect of IL-10 before migration into the inflamed ST, and suggest that this resistance may be attributable to impaired IL-10-dependent STAT3 activation, in association with sustained STAT3 phosphorylation and SOCS1 induction."}
simple1
{"project":"simple1","denotations":[{"id":"T24322","span":{"begin":1388,"end":1393},"obj":"Protein"},{"id":"T24321","span":{"begin":1362,"end":1367},"obj":"Protein"},{"id":"T24320","span":{"begin":1314,"end":1319},"obj":"Protein"},{"id":"T24319","span":{"begin":1298,"end":1303},"obj":"Protein"},{"id":"T24318","span":{"begin":1188,"end":1193},"obj":"Protein"},{"id":"T24317","span":{"begin":1130,"end":1133},"obj":"Protein"},{"id":"T24316","span":{"begin":1087,"end":1090},"obj":"Protein"},{"id":"T24315","span":{"begin":1043,"end":1048},"obj":"Protein"},{"id":"T24314","span":{"begin":1009,"end":1014},"obj":"Protein"},{"id":"T24313","span":{"begin":971,"end":974},"obj":"Protein"},{"id":"T24312","span":{"begin":950,"end":955},"obj":"Protein"},{"id":"T24311","span":{"begin":930,"end":935},"obj":"Protein"},{"id":"T24310","span":{"begin":899,"end":903},"obj":"Protein"},{"id":"T24309","span":{"begin":871,"end":874},"obj":"Protein"},{"id":"T24308","span":{"begin":839,"end":844},"obj":"Protein"},{"id":"T24307","span":{"begin":825,"end":830},"obj":"Protein"},{"id":"T24306","span":{"begin":795,"end":799},"obj":"Protein"},{"id":"T24305","span":{"begin":782,"end":787},"obj":"Protein"},{"id":"T24304","span":{"begin":727,"end":732},"obj":"Protein"},{"id":"T24303","span":{"begin":707,"end":710},"obj":"Protein"},{"id":"T24302","span":{"begin":671,"end":674},"obj":"Protein"},{"id":"T24301","span":{"begin":645,"end":650},"obj":"Protein"},{"id":"T24300","span":{"begin":603,"end":608},"obj":"Protein"},{"id":"T24299","span":{"begin":585,"end":590},"obj":"Protein"},{"id":"T24298","span":{"begin":549,"end":556},"obj":"Protein"},{"id":"T24297","span":{"begin":516,"end":519},"obj":"Protein"},{"id":"T24296","span":{"begin":485,"end":489},"obj":"Protein"},{"id":"T24295","span":{"begin":465,"end":470},"obj":"Protein"},{"id":"T24294","span":{"begin":421,"end":426},"obj":"Protein"},{"id":"T24293","span":{"begin":359,"end":362},"obj":"Protein"},{"id":"T24292","span":{"begin":194,"end":198},"obj":"Protein"},{"id":"T24291","span":{"begin":143,"end":148},"obj":"Protein"},{"id":"T24290","span":{"begin":0,"end":5},"obj":"Protein"}],"text":"IL-10 plays a predominant role in limiting immune and inflammatory responses by regulating the function of both macrophages and Th1 cells [1]. IL-10 inhibits the tyrosine phosphorylation of the CD28 molecule and the subsequent phosphatidylinositol 3-kinase binding in T cells, and thereby directly acts on T cells [24]. In the present study, we found that PB CD4+ T cells from patients with active RA, in the presence of IL-10, are able to produce higher levels of IFN-γ after CD3 and CD28 costimulation than normal CD4+ T cells. Despite high-level IL-10R1 expression and constitutive STAT3 activation, IL-10-induced tyrosine phosphorylation of STAT3 is suppressed in RA CD4+ T cells, in contrast to normal CD4+ T cells, where STAT3 phosphorylation is dose-dependently inducible by IL-10. Serum IL-6 from RA patients induces STAT3 but not STAT1 phosphorylation in normal CD4+ T cells, and exogenous IL-6 induces the resistance to IL-10 inhibition of IFN-γ production. RA CD4+ T cells contain higher levels of SOCS1 but contain lower levels of SOCS3 transcripts in comparison with normal CD4+ T cells. These findings indicate that CD4+ T cells become resistant to the inhibitory effect of IL-10 before migration into the inflamed ST, and suggest that this resistance may be attributable to impaired IL-10-dependent STAT3 activation, in association with sustained STAT3 phosphorylation and SOCS1 induction."}
BioNLP16_DUT
{"project":"BioNLP16_DUT","denotations":[{"id":"T30335","span":{"begin":845,"end":860},"obj":"Phosphorylation"},{"id":"T30334","span":{"begin":557,"end":567},"obj":"Gene_expression"},{"id":"T30333","span":{"begin":733,"end":748},"obj":"Phosphorylation"},{"id":"T30332","span":{"begin":769,"end":778},"obj":"Positive_regulation"},{"id":"T30331","span":{"begin":609,"end":616},"obj":"Positive_regulation"},{"id":"T30330","span":{"begin":654,"end":664},"obj":"Negative_regulation"},{"id":"T30329","span":{"begin":626,"end":641},"obj":"Phosphorylation"},{"id":"T30328","span":{"begin":591,"end":601},"obj":"Positive_regulation"},{"id":"T30327","span":{"begin":440,"end":447},"obj":"Gene_expression"},{"id":"T30326","span":{"begin":171,"end":186},"obj":"Phosphorylation"},{"id":"T30325","span":{"begin":149,"end":157},"obj":"Negative_regulation"},{"id":"T30156","span":{"begin":1388,"end":1393},"obj":"Protein"},{"id":"T30155","span":{"begin":1362,"end":1367},"obj":"Protein"},{"id":"T30154","span":{"begin":1314,"end":1319},"obj":"Protein"},{"id":"T30153","span":{"begin":1298,"end":1303},"obj":"Protein"},{"id":"T30152","span":{"begin":1188,"end":1193},"obj":"Protein"},{"id":"T30151","span":{"begin":1130,"end":1133},"obj":"Protein"},{"id":"T30150","span":{"begin":1087,"end":1090},"obj":"Protein"},{"id":"T30149","span":{"begin":1043,"end":1048},"obj":"Protein"},{"id":"T30148","span":{"begin":1009,"end":1014},"obj":"Protein"},{"id":"T30147","span":{"begin":971,"end":974},"obj":"Protein"},{"id":"T30146","span":{"begin":950,"end":955},"obj":"Protein"},{"id":"T30145","span":{"begin":930,"end":935},"obj":"Protein"},{"id":"T30144","span":{"begin":899,"end":903},"obj":"Protein"},{"id":"T30143","span":{"begin":871,"end":874},"obj":"Protein"},{"id":"T30142","span":{"begin":839,"end":844},"obj":"Protein"},{"id":"T30141","span":{"begin":825,"end":830},"obj":"Protein"},{"id":"T30140","span":{"begin":795,"end":799},"obj":"Protein"},{"id":"T30139","span":{"begin":782,"end":787},"obj":"Protein"},{"id":"T30138","span":{"begin":727,"end":732},"obj":"Protein"},{"id":"T30137","span":{"begin":707,"end":710},"obj":"Protein"},{"id":"T30136","span":{"begin":671,"end":674},"obj":"Protein"},{"id":"T30135","span":{"begin":645,"end":650},"obj":"Protein"},{"id":"T30134","span":{"begin":603,"end":608},"obj":"Protein"},{"id":"T30133","span":{"begin":585,"end":590},"obj":"Protein"},{"id":"T30132","span":{"begin":549,"end":556},"obj":"Protein"},{"id":"T30131","span":{"begin":516,"end":519},"obj":"Protein"},{"id":"T30130","span":{"begin":485,"end":489},"obj":"Protein"},{"id":"T30129","span":{"begin":465,"end":470},"obj":"Protein"},{"id":"T30128","span":{"begin":421,"end":426},"obj":"Protein"},{"id":"T30127","span":{"begin":359,"end":362},"obj":"Protein"},{"id":"T30126","span":{"begin":194,"end":198},"obj":"Protein"},{"id":"T30125","span":{"begin":143,"end":148},"obj":"Protein"},{"id":"T30124","span":{"begin":0,"end":5},"obj":"Protein"},{"id":"T30343","span":{"begin":1320,"end":1330},"obj":"Positive_regulation"},{"id":"T30342","span":{"begin":1394,"end":1403},"obj":"Positive_regulation"},{"id":"T30341","span":{"begin":1289,"end":1297},"obj":"Negative_regulation"},{"id":"T30340","span":{"begin":1368,"end":1383},"obj":"Phosphorylation"},{"id":"T30339","span":{"begin":956,"end":966},"obj":"Gene_expression"},{"id":"T30338","span":{"begin":817,"end":824},"obj":"Positive_regulation"},{"id":"T30337","span":{"begin":904,"end":911},"obj":"Positive_regulation"},{"id":"T30336","span":{"begin":936,"end":946},"obj":"Negative_regulation"}],"relations":[{"id":"R16075","pred":"themeOf","subj":"T30126","obj":"T30326"},{"id":"R16077","pred":"themeOf","subj":"T30129","obj":"T30327"},{"id":"R16099","pred":"themeOf","subj":"T30154","obj":"T30343"},{"id":"R16100","pred":"themeOf","subj":"T30155","obj":"T30340"},{"id":"R16154","pred":"themeOf","subj":"T30326","obj":"T30325"},{"id":"R16167","pred":"themeOf","subj":"T30343","obj":"T30341"},{"id":"R16103","pred":"themeOf","subj":"T30156","obj":"T30342"},{"id":"R16079","pred":"themeOf","subj":"T30132","obj":"T30334"},{"id":"R16080","pred":"themeOf","subj":"T30133","obj":"T30328"},{"id":"R16081","pred":"causeOf","subj":"T30134","obj":"T30331"},{"id":"R16082","pred":"causeOf","subj":"T30134","obj":"T30331"},{"id":"R16084","pred":"themeOf","subj":"T30135","obj":"T30331"},{"id":"R16085","pred":"themeOf","subj":"T30135","obj":"T30329"},{"id":"R16086","pred":"themeOf","subj":"T30138","obj":"T30333"},{"id":"R16157","pred":"themeOf","subj":"T30329","obj":"T30331"},{"id":"R16158","pred":"themeOf","subj":"T30329","obj":"T30330"},{"id":"R16160","pred":"themeOf","subj":"T30333","obj":"T30332"},{"id":"R16161","pred":"themeOf","subj":"T30334","obj":"T30330"},{"id":"R16087","pred":"causeOf","subj":"T30139","obj":"T30332"},{"id":"R16088","pred":"causeOf","subj":"T30140","obj":"T30338"},{"id":"R16089","pred":"causeOf","subj":"T30140","obj":"T30338"},{"id":"R16090","pred":"themeOf","subj":"T30141","obj":"T30335"},{"id":"R16092","pred":"themeOf","subj":"T30142","obj":"T30335"},{"id":"R16093","pred":"themeOf","subj":"T30144","obj":"T30337"},{"id":"R16094","pred":"themeOf","subj":"T30145","obj":"T30336"},{"id":"R16095","pred":"themeOf","subj":"T30146","obj":"T30339"},{"id":"R16162","pred":"themeOf","subj":"T30335","obj":"T30338"},{"id":"R16163","pred":"themeOf","subj":"T30335","obj":"T30338"},{"id":"R16166","pred":"themeOf","subj":"T30339","obj":"T30336"}],"text":"IL-10 plays a predominant role in limiting immune and inflammatory responses by regulating the function of both macrophages and Th1 cells [1]. IL-10 inhibits the tyrosine phosphorylation of the CD28 molecule and the subsequent phosphatidylinositol 3-kinase binding in T cells, and thereby directly acts on T cells [24]. In the present study, we found that PB CD4+ T cells from patients with active RA, in the presence of IL-10, are able to produce higher levels of IFN-γ after CD3 and CD28 costimulation than normal CD4+ T cells. Despite high-level IL-10R1 expression and constitutive STAT3 activation, IL-10-induced tyrosine phosphorylation of STAT3 is suppressed in RA CD4+ T cells, in contrast to normal CD4+ T cells, where STAT3 phosphorylation is dose-dependently inducible by IL-10. Serum IL-6 from RA patients induces STAT3 but not STAT1 phosphorylation in normal CD4+ T cells, and exogenous IL-6 induces the resistance to IL-10 inhibition of IFN-γ production. RA CD4+ T cells contain higher levels of SOCS1 but contain lower levels of SOCS3 transcripts in comparison with normal CD4+ T cells. These findings indicate that CD4+ T cells become resistant to the inhibitory effect of IL-10 before migration into the inflamed ST, and suggest that this resistance may be attributable to impaired IL-10-dependent STAT3 activation, in association with sustained STAT3 phosphorylation and SOCS1 induction."}
BioNLP16_Messiy
{"project":"BioNLP16_Messiy","denotations":[{"id":"T26704","span":{"begin":1394,"end":1403},"obj":"Positive_regulation"},{"id":"T26703","span":{"begin":1304,"end":1313},"obj":"Regulation"},{"id":"T26702","span":{"begin":1273,"end":1285},"obj":"Positive_regulation"},{"id":"T26701","span":{"begin":1352,"end":1361},"obj":"Positive_regulation"},{"id":"T26700","span":{"begin":1289,"end":1297},"obj":"Negative_regulation"},{"id":"T26699","span":{"begin":1368,"end":1383},"obj":"Phosphorylation"},{"id":"T26698","span":{"begin":1320,"end":1330},"obj":"Positive_regulation"},{"id":"T26697","span":{"begin":1049,"end":1060},"obj":"Transcription"},{"id":"T26696","span":{"begin":904,"end":911},"obj":"Positive_regulation"},{"id":"T26695","span":{"begin":956,"end":966},"obj":"Gene_expression"},{"id":"T26694","span":{"begin":916,"end":926},"obj":"Positive_regulation"},{"id":"T26693","span":{"begin":889,"end":898},"obj":"Positive_regulation"},{"id":"T26692","span":{"begin":936,"end":946},"obj":"Negative_regulation"},{"id":"T26691","span":{"begin":845,"end":860},"obj":"Phosphorylation"},{"id":"T26690","span":{"begin":817,"end":824},"obj":"Positive_regulation"},{"id":"T26689","span":{"begin":733,"end":748},"obj":"Phosphorylation"},{"id":"T26688","span":{"begin":591,"end":601},"obj":"Positive_regulation"},{"id":"T26687","span":{"begin":654,"end":664},"obj":"Negative_regulation"},{"id":"T26686","span":{"begin":626,"end":641},"obj":"Phosphorylation"},{"id":"T26685","span":{"begin":557,"end":567},"obj":"Gene_expression"},{"id":"T26684","span":{"begin":769,"end":778},"obj":"Positive_regulation"},{"id":"T26683","span":{"begin":609,"end":616},"obj":"Positive_regulation"},{"id":"T26682","span":{"begin":440,"end":447},"obj":"Gene_expression"},{"id":"T26681","span":{"begin":149,"end":157},"obj":"Negative_regulation"},{"id":"T26512","span":{"begin":1388,"end":1393},"obj":"Protein"},{"id":"T26511","span":{"begin":1362,"end":1367},"obj":"Protein"},{"id":"T26510","span":{"begin":1314,"end":1319},"obj":"Protein"},{"id":"T26509","span":{"begin":1298,"end":1303},"obj":"Protein"},{"id":"T26508","span":{"begin":1188,"end":1193},"obj":"Protein"},{"id":"T26507","span":{"begin":1130,"end":1133},"obj":"Protein"},{"id":"T26506","span":{"begin":1087,"end":1090},"obj":"Protein"},{"id":"T26505","span":{"begin":1043,"end":1048},"obj":"Protein"},{"id":"T26504","span":{"begin":1009,"end":1014},"obj":"Protein"},{"id":"T26503","span":{"begin":971,"end":974},"obj":"Protein"},{"id":"T26502","span":{"begin":950,"end":955},"obj":"Protein"},{"id":"T26501","span":{"begin":930,"end":935},"obj":"Protein"},{"id":"T26500","span":{"begin":899,"end":903},"obj":"Protein"},{"id":"T26499","span":{"begin":871,"end":874},"obj":"Protein"},{"id":"T26498","span":{"begin":839,"end":844},"obj":"Protein"},{"id":"T26497","span":{"begin":825,"end":830},"obj":"Protein"},{"id":"T26496","span":{"begin":795,"end":799},"obj":"Protein"},{"id":"T26495","span":{"begin":782,"end":787},"obj":"Protein"},{"id":"T26494","span":{"begin":727,"end":732},"obj":"Protein"},{"id":"T26493","span":{"begin":707,"end":710},"obj":"Protein"},{"id":"T26492","span":{"begin":671,"end":674},"obj":"Protein"},{"id":"T26491","span":{"begin":645,"end":650},"obj":"Protein"},{"id":"T26490","span":{"begin":603,"end":608},"obj":"Protein"},{"id":"T26489","span":{"begin":585,"end":590},"obj":"Protein"},{"id":"T26488","span":{"begin":549,"end":556},"obj":"Protein"},{"id":"T26487","span":{"begin":516,"end":519},"obj":"Protein"},{"id":"T26486","span":{"begin":485,"end":489},"obj":"Protein"},{"id":"T26485","span":{"begin":465,"end":470},"obj":"Protein"},{"id":"T26484","span":{"begin":421,"end":426},"obj":"Protein"},{"id":"T26483","span":{"begin":359,"end":362},"obj":"Protein"},{"id":"T26482","span":{"begin":194,"end":198},"obj":"Protein"},{"id":"T26481","span":{"begin":143,"end":148},"obj":"Protein"},{"id":"T26480","span":{"begin":0,"end":5},"obj":"Protein"}],"relations":[{"id":"R13451","pred":"themeOf","subj":"T26481","obj":"T26681"},{"id":"R13452","pred":"themeOf","subj":"T26485","obj":"T26682"},{"id":"R13453","pred":"themeOf","subj":"T26488","obj":"T26685"},{"id":"R13454","pred":"themeOf","subj":"T26489","obj":"T26688"},{"id":"R13455","pred":"causeOf","subj":"T26490","obj":"T26683"},{"id":"R13456","pred":"themeOf","subj":"T26491","obj":"T26686"},{"id":"R13457","pred":"themeOf","subj":"T26494","obj":"T26689"},{"id":"R13458","pred":"causeOf","subj":"T26496","obj":"T26690"},{"id":"R13460","pred":"causeOf","subj":"T26496","obj":"T26690"},{"id":"R13462","pred":"themeOf","subj":"T26497","obj":"T26691"},{"id":"R13464","pred":"themeOf","subj":"T26498","obj":"T26691"},{"id":"R13467","pred":"themeOf","subj":"T26500","obj":"T26693"},{"id":"R13468","pred":"causeOf","subj":"T26500","obj":"T26696"},{"id":"R13470","pred":"causeOf","subj":"T26500","obj":"T26696"},{"id":"R13471","pred":"themeOf","subj":"T26501","obj":"T26692"},{"id":"R13473","pred":"themeOf","subj":"T26502","obj":"T26695"},{"id":"R13474","pred":"themeOf","subj":"T26505","obj":"T26697"},{"id":"R13476","pred":"causeOf","subj":"T26509","obj":"T26703"},{"id":"R13477","pred":"themeOf","subj":"T26510","obj":"T26698"},{"id":"R13479","pred":"themeOf","subj":"T26511","obj":"T26699"},{"id":"R13481","pred":"themeOf","subj":"T26512","obj":"T26704"},{"id":"R13552","pred":"themeOf","subj":"T26686","obj":"T26683"},{"id":"R13555","pred":"themeOf","subj":"T26686","obj":"T26687"},{"id":"R13556","pred":"themeOf","subj":"T26689","obj":"T26684"},{"id":"R13558","pred":"themeOf","subj":"T26691","obj":"T26690"},{"id":"R13560","pred":"themeOf","subj":"T26691","obj":"T26690"},{"id":"R13561","pred":"themeOf","subj":"T26692","obj":"T26694"},{"id":"R13563","pred":"themeOf","subj":"T26692","obj":"T26694"},{"id":"R13564","pred":"themeOf","subj":"T26694","obj":"T26696"},{"id":"R13566","pred":"themeOf","subj":"T26694","obj":"T26696"},{"id":"R13567","pred":"themeOf","subj":"T26695","obj":"T26692"},{"id":"R13568","pred":"themeOf","subj":"T26698","obj":"T26702"},{"id":"R13570","pred":"themeOf","subj":"T26698","obj":"T26700"},{"id":"R13571","pred":"themeOf","subj":"T26698","obj":"T26703"},{"id":"R13572","pred":"themeOf","subj":"T26699","obj":"T26701"}],"text":"IL-10 plays a predominant role in limiting immune and inflammatory responses by regulating the function of both macrophages and Th1 cells [1]. IL-10 inhibits the tyrosine phosphorylation of the CD28 molecule and the subsequent phosphatidylinositol 3-kinase binding in T cells, and thereby directly acts on T cells [24]. In the present study, we found that PB CD4+ T cells from patients with active RA, in the presence of IL-10, are able to produce higher levels of IFN-γ after CD3 and CD28 costimulation than normal CD4+ T cells. Despite high-level IL-10R1 expression and constitutive STAT3 activation, IL-10-induced tyrosine phosphorylation of STAT3 is suppressed in RA CD4+ T cells, in contrast to normal CD4+ T cells, where STAT3 phosphorylation is dose-dependently inducible by IL-10. Serum IL-6 from RA patients induces STAT3 but not STAT1 phosphorylation in normal CD4+ T cells, and exogenous IL-6 induces the resistance to IL-10 inhibition of IFN-γ production. RA CD4+ T cells contain higher levels of SOCS1 but contain lower levels of SOCS3 transcripts in comparison with normal CD4+ T cells. These findings indicate that CD4+ T cells become resistant to the inhibitory effect of IL-10 before migration into the inflamed ST, and suggest that this resistance may be attributable to impaired IL-10-dependent STAT3 activation, in association with sustained STAT3 phosphorylation and SOCS1 induction."}
DLUT931
{"project":"DLUT931","denotations":[{"id":"T28796","span":{"begin":1352,"end":1361},"obj":"Positive_regulation"},{"id":"T28795","span":{"begin":1394,"end":1403},"obj":"Positive_regulation"},{"id":"T28794","span":{"begin":1368,"end":1383},"obj":"Phosphorylation"},{"id":"T28793","span":{"begin":1320,"end":1330},"obj":"Positive_regulation"},{"id":"T28792","span":{"begin":1027,"end":1032},"obj":"Positive_regulation"},{"id":"T28791","span":{"begin":1049,"end":1060},"obj":"Transcription"},{"id":"T28790","span":{"begin":992,"end":998},"obj":"Positive_regulation"},{"id":"T28789","span":{"begin":904,"end":911},"obj":"Positive_regulation"},{"id":"T28788","span":{"begin":916,"end":926},"obj":"Positive_regulation"},{"id":"T28787","span":{"begin":936,"end":946},"obj":"Negative_regulation"},{"id":"T28786","span":{"begin":817,"end":824},"obj":"Positive_regulation"},{"id":"T28785","span":{"begin":956,"end":966},"obj":"Gene_expression"},{"id":"T28784","span":{"begin":845,"end":860},"obj":"Phosphorylation"},{"id":"T28783","span":{"begin":609,"end":616},"obj":"Positive_regulation"},{"id":"T28782","span":{"begin":538,"end":548},"obj":"Positive_regulation"},{"id":"T28781","span":{"begin":769,"end":778},"obj":"Positive_regulation"},{"id":"T28780","span":{"begin":733,"end":748},"obj":"Phosphorylation"},{"id":"T28779","span":{"begin":626,"end":641},"obj":"Phosphorylation"},{"id":"T28778","span":{"begin":557,"end":567},"obj":"Gene_expression"},{"id":"T28777","span":{"begin":440,"end":447},"obj":"Gene_expression"},{"id":"T28776","span":{"begin":149,"end":157},"obj":"Negative_regulation"},{"id":"T28775","span":{"begin":171,"end":186},"obj":"Phosphorylation"},{"id":"T28596","span":{"begin":1388,"end":1393},"obj":"Protein"},{"id":"T28595","span":{"begin":1362,"end":1367},"obj":"Protein"},{"id":"T28594","span":{"begin":1314,"end":1319},"obj":"Protein"},{"id":"T28593","span":{"begin":1298,"end":1303},"obj":"Protein"},{"id":"T28592","span":{"begin":1188,"end":1193},"obj":"Protein"},{"id":"T28591","span":{"begin":1130,"end":1133},"obj":"Protein"},{"id":"T28590","span":{"begin":1087,"end":1090},"obj":"Protein"},{"id":"T28589","span":{"begin":1043,"end":1048},"obj":"Protein"},{"id":"T28588","span":{"begin":1009,"end":1014},"obj":"Protein"},{"id":"T28587","span":{"begin":971,"end":974},"obj":"Protein"},{"id":"T28586","span":{"begin":950,"end":955},"obj":"Protein"},{"id":"T28585","span":{"begin":930,"end":935},"obj":"Protein"},{"id":"T28584","span":{"begin":899,"end":903},"obj":"Protein"},{"id":"T28583","span":{"begin":871,"end":874},"obj":"Protein"},{"id":"T28582","span":{"begin":839,"end":844},"obj":"Protein"},{"id":"T28581","span":{"begin":825,"end":830},"obj":"Protein"},{"id":"T28580","span":{"begin":795,"end":799},"obj":"Protein"},{"id":"T28579","span":{"begin":782,"end":787},"obj":"Protein"},{"id":"T28578","span":{"begin":727,"end":732},"obj":"Protein"},{"id":"T28577","span":{"begin":707,"end":710},"obj":"Protein"},{"id":"T28576","span":{"begin":671,"end":674},"obj":"Protein"},{"id":"T28575","span":{"begin":645,"end":650},"obj":"Protein"},{"id":"T28574","span":{"begin":603,"end":608},"obj":"Protein"},{"id":"T28573","span":{"begin":585,"end":590},"obj":"Protein"},{"id":"T28572","span":{"begin":549,"end":556},"obj":"Protein"},{"id":"T28571","span":{"begin":516,"end":519},"obj":"Protein"},{"id":"T28570","span":{"begin":485,"end":489},"obj":"Protein"},{"id":"T28569","span":{"begin":465,"end":470},"obj":"Protein"},{"id":"T28568","span":{"begin":421,"end":426},"obj":"Protein"},{"id":"T28567","span":{"begin":359,"end":362},"obj":"Protein"},{"id":"T28566","span":{"begin":194,"end":198},"obj":"Protein"},{"id":"T28565","span":{"begin":143,"end":148},"obj":"Protein"},{"id":"T28564","span":{"begin":0,"end":5},"obj":"Protein"}],"relations":[{"id":"R15368","pred":"themeOf","subj":"T28575","obj":"T28779"},{"id":"R15370","pred":"themeOf","subj":"T28578","obj":"T28780"},{"id":"R15371","pred":"causeOf","subj":"T28579","obj":"T28781"},{"id":"R15372","pred":"causeOf","subj":"T28580","obj":"T28786"},{"id":"R15375","pred":"themeOf","subj":"T28581","obj":"T28784"},{"id":"R15377","pred":"causeOf","subj":"T28584","obj":"T28789"},{"id":"R15378","pred":"themeOf","subj":"T28586","obj":"T28785"},{"id":"R15379","pred":"themeOf","subj":"T28588","obj":"T28790"},{"id":"R15380","pred":"themeOf","subj":"T28589","obj":"T28791"},{"id":"R15383","pred":"themeOf","subj":"T28594","obj":"T28793"},{"id":"R15385","pred":"themeOf","subj":"T28595","obj":"T28794"},{"id":"R15386","pred":"themeOf","subj":"T28596","obj":"T28795"},{"id":"R15445","pred":"themeOf","subj":"T28775","obj":"T28776"},{"id":"R15447","pred":"themeOf","subj":"T28778","obj":"T28782"},{"id":"R15449","pred":"themeOf","subj":"T28779","obj":"T28783"},{"id":"R15450","pred":"themeOf","subj":"T28780","obj":"T28781"},{"id":"R15453","pred":"themeOf","subj":"T28784","obj":"T28786"},{"id":"R15454","pred":"themeOf","subj":"T28784","obj":"T28786"},{"id":"R15456","pred":"themeOf","subj":"T28785","obj":"T28787"},{"id":"R15458","pred":"themeOf","subj":"T28787","obj":"T28788"},{"id":"R15459","pred":"themeOf","subj":"T28788","obj":"T28789"},{"id":"R15461","pred":"themeOf","subj":"T28791","obj":"T28792"},{"id":"R15463","pred":"themeOf","subj":"T28794","obj":"T28796"},{"id":"R15358","pred":"causeOf","subj":"T28565","obj":"T28776"},{"id":"R15359","pred":"themeOf","subj":"T28566","obj":"T28775"},{"id":"R15361","pred":"themeOf","subj":"T28569","obj":"T28777"},{"id":"R15364","pred":"themeOf","subj":"T28572","obj":"T28778"},{"id":"R15366","pred":"causeOf","subj":"T28574","obj":"T28783"},{"id":"R15363","pred":"themeOf","subj":"T28570","obj":"T28777"},{"id":"R15373","pred":"causeOf","subj":"T28580","obj":"T28786"},{"id":"R15376","pred":"themeOf","subj":"T28582","obj":"T28784"}],"text":"IL-10 plays a predominant role in limiting immune and inflammatory responses by regulating the function of both macrophages and Th1 cells [1]. IL-10 inhibits the tyrosine phosphorylation of the CD28 molecule and the subsequent phosphatidylinositol 3-kinase binding in T cells, and thereby directly acts on T cells [24]. In the present study, we found that PB CD4+ T cells from patients with active RA, in the presence of IL-10, are able to produce higher levels of IFN-γ after CD3 and CD28 costimulation than normal CD4+ T cells. Despite high-level IL-10R1 expression and constitutive STAT3 activation, IL-10-induced tyrosine phosphorylation of STAT3 is suppressed in RA CD4+ T cells, in contrast to normal CD4+ T cells, where STAT3 phosphorylation is dose-dependently inducible by IL-10. Serum IL-6 from RA patients induces STAT3 but not STAT1 phosphorylation in normal CD4+ T cells, and exogenous IL-6 induces the resistance to IL-10 inhibition of IFN-γ production. RA CD4+ T cells contain higher levels of SOCS1 but contain lower levels of SOCS3 transcripts in comparison with normal CD4+ T cells. These findings indicate that CD4+ T cells become resistant to the inhibitory effect of IL-10 before migration into the inflamed ST, and suggest that this resistance may be attributable to impaired IL-10-dependent STAT3 activation, in association with sustained STAT3 phosphorylation and SOCS1 induction."}
bionlp-st-ge-2016-test-ihmc
{"project":"bionlp-st-ge-2016-test-ihmc","denotations":[{"id":"T30112","span":{"begin":789,"end":883},"obj":"Gene_expression"},{"id":"T30111","span":{"begin":789,"end":883},"obj":"Positive_regulation"},{"id":"T30105","span":{"begin":727,"end":748},"obj":"Phosphorylation"},{"id":"T30099","span":{"begin":158,"end":207},"obj":"Phosphorylation"},{"id":"T30067","span":{"begin":1289,"end":1393},"obj":"Positive_regulation"},{"id":"T30066","span":{"begin":947,"end":966},"obj":"Gene_expression"},{"id":"T30061","span":{"begin":1289,"end":1313},"obj":"Negative_regulation"},{"id":"T30050","span":{"begin":572,"end":602},"obj":"Positive_regulation"},{"id":"T30045","span":{"begin":1352,"end":1383},"obj":"Phosphorylation"},{"id":"T30040","span":{"begin":603,"end":650},"obj":"Phosphorylation"},{"id":"T30037","span":{"begin":485,"end":503},"obj":"Positive_regulation"},{"id":"T30035","span":{"begin":1289,"end":1393},"obj":"Regulation"},{"id":"T30029","span":{"begin":839,"end":860},"obj":"Phosphorylation"},{"id":"T30026","span":{"begin":930,"end":966},"obj":"Negative_regulation"},{"id":"T30007","span":{"begin":950,"end":955},"obj":"Protein"},{"id":"T30005","span":{"begin":968,"end":970},"obj":"Protein"},{"id":"T30003","span":{"begin":782,"end":787},"obj":"Protein"},{"id":"T30002","span":{"begin":668,"end":670},"obj":"Protein"},{"id":"T29999","span":{"begin":1314,"end":1319},"obj":"Protein"},{"id":"T29994","span":{"begin":356,"end":358},"obj":"Protein"},{"id":"T29988","span":{"begin":1185,"end":1193},"obj":"Protein"},{"id":"T29986","span":{"begin":504,"end":528},"obj":"Entity"},{"id":"T29985","span":{"begin":485,"end":489},"obj":"Protein"},{"id":"T29984","span":{"begin":603,"end":616},"obj":"Protein"},{"id":"T29979","span":{"begin":187,"end":207},"obj":"Protein"},{"id":"T29972","span":{"begin":268,"end":275},"obj":"Entity"},{"id":"T29965","span":{"begin":825,"end":860},"obj":"Protein"},{"id":"T29956","span":{"begin":1289,"end":1313},"obj":"Protein"},{"id":"T29945","span":{"begin":889,"end":903},"obj":"Protein"},{"id":"T29936","span":{"begin":668,"end":683},"obj":"Entity"},{"id":"T29919","span":{"begin":864,"end":883},"obj":"Entity"},{"id":"T29903","span":{"begin":162,"end":170},"obj":"Entity"},{"id":"T29800","span":{"begin":356,"end":401},"obj":"Entity"},{"id":"T29799","span":{"begin":1009,"end":1014},"obj":"Protein"},{"id":"T29705","span":{"begin":727,"end":732},"obj":"Protein"},{"id":"T29704","span":{"begin":0,"end":5},"obj":"Protein"},{"id":"T29699","span":{"begin":1388,"end":1393},"obj":"Protein"},{"id":"T29695","span":{"begin":477,"end":480},"obj":"Protein"},{"id":"T29691","span":{"begin":585,"end":590},"obj":"Protein"},{"id":"T29688","span":{"begin":1216,"end":1232},"obj":"Protein"},{"id":"T29896","span":{"begin":839,"end":844},"obj":"Protein"},{"id":"T29685","span":{"begin":549,"end":556},"obj":"Protein"},{"id":"T29682","span":{"begin":112,"end":123},"obj":"Entity"},{"id":"T29673","span":{"begin":968,"end":983},"obj":"Entity"},{"id":"T29672","span":{"begin":789,"end":799},"obj":"Protein"},{"id":"T29744","span":{"begin":128,"end":137},"obj":"Entity"},{"id":"T29742","span":{"begin":805,"end":807},"obj":"Protein"},{"id":"T29734","span":{"begin":1043,"end":1048},"obj":"Protein"},{"id":"T29732","span":{"begin":465,"end":470},"obj":"Protein"},{"id":"T29726","span":{"begin":712,"end":719},"obj":"Entity"},{"id":"T29716","span":{"begin":421,"end":427},"obj":"Protein"},{"id":"T29772","span":{"begin":1130,"end":1142},"obj":"Entity"},{"id":"T29769","span":{"begin":306,"end":318},"obj":"Entity"},{"id":"T29760","span":{"begin":617,"end":625},"obj":"Entity"},{"id":"T29819","span":{"begin":1043,"end":1060},"obj":"Protein"},{"id":"T29858","span":{"begin":700,"end":710},"obj":"Protein"},{"id":"T29853","span":{"begin":391,"end":400},"obj":"Protein"},{"id":"T29851","span":{"begin":930,"end":935},"obj":"Protein"},{"id":"T29875","span":{"begin":143,"end":148},"obj":"Protein"},{"id":"T29873","span":{"begin":642,"end":650},"obj":"Protein"},{"id":"T29872","span":{"begin":1362,"end":1367},"obj":"Protein"},{"id":"T29871","span":{"begin":1080,"end":1099},"obj":"Entity"}],"relations":[{"id":"R15942","pred":"causeOf","subj":"T29672","obj":"T30111"},{"id":"R15950","pred":"themeOf","subj":"T29691","obj":"T30050"},{"id":"R15959","pred":"themeOf","subj":"T29705","obj":"T30105"},{"id":"R15970","pred":"partOf","subj":"T29760","obj":"T29873"},{"id":"R15975","pred":"siteOf","subj":"T29760","obj":"T30040"},{"id":"R15989","pred":"causeOf","subj":"T29851","obj":"T30026"},{"id":"R15999","pred":"themeOf","subj":"T29872","obj":"T30045"},{"id":"R16000","pred":"themeOf","subj":"T29873","obj":"T30040"},{"id":"R16009","pred":"themeOf","subj":"T29896","obj":"T30029"},{"id":"R16013","pred":"partOf","subj":"T29903","obj":"T29979"},{"id":"R16014","pred":"themeOf","subj":"T29999","obj":"T30067"},{"id":"R16016","pred":"siteOf","subj":"T29903","obj":"T30099"},{"id":"R16019","pred":"themeOf","subj":"T30007","obj":"T30066"},{"id":"R16040","pred":"themeOf","subj":"T30066","obj":"T30026"},{"id":"R16041","pred":"themeOf","subj":"T30067","obj":"T30035"},{"id":"R16052","pred":"causeOf","subj":"T29956","obj":"T30035"},{"id":"R16055","pred":"themeOf","subj":"T29956","obj":"T30061"},{"id":"R16062","pred":"themeOf","subj":"T29965","obj":"T30111"},{"id":"R16063","pred":"themeOf","subj":"T29965","obj":"T30112"},{"id":"R16067","pred":"themeOf","subj":"T29979","obj":"T30099"},{"id":"R16068","pred":"themeOf","subj":"T29985","obj":"T30037"}],"text":"IL-10 plays a predominant role in limiting immune and inflammatory responses by regulating the function of both macrophages and Th1 cells [1]. IL-10 inhibits the tyrosine phosphorylation of the CD28 molecule and the subsequent phosphatidylinositol 3-kinase binding in T cells, and thereby directly acts on T cells [24]. In the present study, we found that PB CD4+ T cells from patients with active RA, in the presence of IL-10, are able to produce higher levels of IFN-γ after CD3 and CD28 costimulation than normal CD4+ T cells. Despite high-level IL-10R1 expression and constitutive STAT3 activation, IL-10-induced tyrosine phosphorylation of STAT3 is suppressed in RA CD4+ T cells, in contrast to normal CD4+ T cells, where STAT3 phosphorylation is dose-dependently inducible by IL-10. Serum IL-6 from RA patients induces STAT3 but not STAT1 phosphorylation in normal CD4+ T cells, and exogenous IL-6 induces the resistance to IL-10 inhibition of IFN-γ production. RA CD4+ T cells contain higher levels of SOCS1 but contain lower levels of SOCS3 transcripts in comparison with normal CD4+ T cells. These findings indicate that CD4+ T cells become resistant to the inhibitory effect of IL-10 before migration into the inflamed ST, and suggest that this resistance may be attributable to impaired IL-10-dependent STAT3 activation, in association with sustained STAT3 phosphorylation and SOCS1 induction."}
bionlp-st-ge-2016-spacy-parsed
{"project":"bionlp-st-ge-2016-spacy-parsed","denotations":[{"id":"T27186","span":{"begin":1368,"end":1383},"obj":"NN"},{"id":"T27185","span":{"begin":1362,"end":1367},"obj":"NNP"},{"id":"T27184","span":{"begin":1352,"end":1361},"obj":"VBN"},{"id":"T27181","span":{"begin":1332,"end":1334},"obj":"IN"},{"id":"T27180","span":{"begin":1330,"end":1331},"obj":","},{"id":"T27179","span":{"begin":1320,"end":1330},"obj":"NN"},{"id":"T27178","span":{"begin":1314,"end":1319},"obj":"CD"},{"id":"T27177","span":{"begin":1298,"end":1313},"obj":"JJ"},{"id":"T27176","span":{"begin":1289,"end":1297},"obj":"VBN"},{"id":"T27175","span":{"begin":1286,"end":1288},"obj":"TO"},{"id":"T27174","span":{"begin":1273,"end":1285},"obj":"JJ"},{"id":"T27173","span":{"begin":1270,"end":1272},"obj":"VB"},{"id":"T27172","span":{"begin":1266,"end":1269},"obj":"MD"},{"id":"T27171","span":{"begin":1255,"end":1265},"obj":"NN"},{"id":"T27170","span":{"begin":1250,"end":1254},"obj":"DT"},{"id":"T27169","span":{"begin":1245,"end":1249},"obj":"IN"},{"id":"T27168","span":{"begin":1237,"end":1244},"obj":"VBP"},{"id":"T27167","span":{"begin":1233,"end":1236},"obj":"CC"},{"id":"T27166","span":{"begin":1231,"end":1232},"obj":","},{"id":"T27165","span":{"begin":1229,"end":1231},"obj":"NNP"},{"id":"T27164","span":{"begin":1220,"end":1228},"obj":"JJ"},{"id":"T27163","span":{"begin":1216,"end":1219},"obj":"DT"},{"id":"T27162","span":{"begin":1211,"end":1215},"obj":"IN"},{"id":"T27161","span":{"begin":1201,"end":1210},"obj":"NN"},{"id":"T27160","span":{"begin":1194,"end":1200},"obj":"IN"},{"id":"T27159","span":{"begin":1188,"end":1193},"obj":"NN"},{"id":"T27158","span":{"begin":1185,"end":1187},"obj":"IN"},{"id":"T27157","span":{"begin":1178,"end":1184},"obj":"NN"},{"id":"T27156","span":{"begin":1167,"end":1177},"obj":"JJ"},{"id":"T27155","span":{"begin":1163,"end":1166},"obj":"DT"},{"id":"T27154","span":{"begin":1160,"end":1162},"obj":"TO"},{"id":"T27153","span":{"begin":1150,"end":1159},"obj":"JJ"},{"id":"T27152","span":{"begin":1143,"end":1149},"obj":"VBP"},{"id":"T27151","span":{"begin":1137,"end":1142},"obj":"NNS"},{"id":"T27150","span":{"begin":1135,"end":1136},"obj":"NNP"},{"id":"T27149","span":{"begin":1133,"end":1134},"obj":"CD"},{"id":"T27148","span":{"begin":1130,"end":1133},"obj":"CD"},{"id":"T27147","span":{"begin":1125,"end":1129},"obj":"IN"},{"id":"T27146","span":{"begin":1116,"end":1124},"obj":"VBP"},{"id":"T27145","span":{"begin":1107,"end":1115},"obj":"NNS"},{"id":"T27144","span":{"begin":1101,"end":1106},"obj":"DT"},{"id":"T27143","span":{"begin":1099,"end":1100},"obj":"."},{"id":"T27142","span":{"begin":1094,"end":1099},"obj":"NNS"},{"id":"T27141","span":{"begin":1092,"end":1093},"obj":"NNP"},{"id":"T27140","span":{"begin":1090,"end":1091},"obj":"CD"},{"id":"T27139","span":{"begin":1087,"end":1090},"obj":"NNP"},{"id":"T27138","span":{"begin":1080,"end":1086},"obj":"JJ"},{"id":"T27137","span":{"begin":1075,"end":1079},"obj":"IN"},{"id":"T27136","span":{"begin":1064,"end":1074},"obj":"NN"},{"id":"T27135","span":{"begin":1061,"end":1063},"obj":"IN"},{"id":"T27134","span":{"begin":1049,"end":1060},"obj":"NNS"},{"id":"T27133","span":{"begin":1043,"end":1048},"obj":"CD"},{"id":"T27132","span":{"begin":1040,"end":1042},"obj":"IN"},{"id":"T27131","span":{"begin":1033,"end":1039},"obj":"NNS"},{"id":"T27130","span":{"begin":1027,"end":1032},"obj":"JJR"},{"id":"T27129","span":{"begin":1019,"end":1026},"obj":"VBP"},{"id":"T27128","span":{"begin":1015,"end":1018},"obj":"CC"},{"id":"T27127","span":{"begin":1009,"end":1014},"obj":"CD"},{"id":"T27126","span":{"begin":1006,"end":1008},"obj":"IN"},{"id":"T27125","span":{"begin":999,"end":1005},"obj":"NNS"},{"id":"T27124","span":{"begin":992,"end":998},"obj":"JJR"},{"id":"T27123","span":{"begin":984,"end":991},"obj":"VBP"},{"id":"T27122","span":{"begin":978,"end":983},"obj":"NNS"},{"id":"T27121","span":{"begin":976,"end":977},"obj":"NNP"},{"id":"T27120","span":{"begin":974,"end":975},"obj":"VBD"},{"id":"T27119","span":{"begin":971,"end":974},"obj":"NNP"},{"id":"T27118","span":{"begin":968,"end":970},"obj":"NNP"},{"id":"T27117","span":{"begin":966,"end":967},"obj":"."},{"id":"T27116","span":{"begin":956,"end":966},"obj":"NN"},{"id":"T27115","span":{"begin":950,"end":955},"obj":"JJ"},{"id":"T27114","span":{"begin":947,"end":949},"obj":"IN"},{"id":"T27113","span":{"begin":936,"end":946},"obj":"NN"},{"id":"T27112","span":{"begin":930,"end":935},"obj":"NNP"},{"id":"T27111","span":{"begin":927,"end":929},"obj":"TO"},{"id":"T27110","span":{"begin":916,"end":926},"obj":"NN"},{"id":"T27109","span":{"begin":912,"end":915},"obj":"DT"},{"id":"T27108","span":{"begin":904,"end":911},"obj":"VBZ"},{"id":"T27107","span":{"begin":899,"end":903},"obj":"NN"},{"id":"T27106","span":{"begin":889,"end":898},"obj":"JJ"},{"id":"T27105","span":{"begin":885,"end":888},"obj":"CC"},{"id":"T27104","span":{"begin":883,"end":884},"obj":","},{"id":"T27103","span":{"begin":878,"end":883},"obj":"NNS"},{"id":"T27102","span":{"begin":876,"end":877},"obj":"NNP"},{"id":"T27101","span":{"begin":874,"end":875},"obj":"CD"},{"id":"T27100","span":{"begin":871,"end":874},"obj":"NNP"},{"id":"T27099","span":{"begin":864,"end":870},"obj":"JJ"},{"id":"T27098","span":{"begin":861,"end":863},"obj":"IN"},{"id":"T27097","span":{"begin":845,"end":860},"obj":"NN"},{"id":"T27096","span":{"begin":839,"end":844},"obj":"CD"},{"id":"T27095","span":{"begin":835,"end":838},"obj":"RB"},{"id":"T27094","span":{"begin":831,"end":834},"obj":"CC"},{"id":"T27093","span":{"begin":825,"end":830},"obj":"CD"},{"id":"T27092","span":{"begin":817,"end":824},"obj":"VBZ"},{"id":"T27091","span":{"begin":808,"end":816},"obj":"NNS"},{"id":"T27090","span":{"begin":805,"end":807},"obj":"NNP"},{"id":"T27089","span":{"begin":800,"end":804},"obj":"IN"},{"id":"T27088","span":{"begin":795,"end":799},"obj":"NNP"},{"id":"T27072","span":{"begin":700,"end":706},"obj":"JJ"},{"id":"T27071","span":{"begin":697,"end":699},"obj":"TO"},{"id":"T27070","span":{"begin":688,"end":696},"obj":"NN"},{"id":"T27069","span":{"begin":685,"end":687},"obj":"IN"},{"id":"T27068","span":{"begin":683,"end":684},"obj":","},{"id":"T27067","span":{"begin":678,"end":683},"obj":"NNS"},{"id":"T27066","span":{"begin":676,"end":677},"obj":"NNP"},{"id":"T27065","span":{"begin":674,"end":675},"obj":"VBD"},{"id":"T27064","span":{"begin":671,"end":674},"obj":"NNP"},{"id":"T27063","span":{"begin":668,"end":670},"obj":"NNP"},{"id":"T27062","span":{"begin":665,"end":667},"obj":"IN"},{"id":"T27061","span":{"begin":654,"end":664},"obj":"VBN"},{"id":"T27060","span":{"begin":651,"end":653},"obj":"VBZ"},{"id":"T27059","span":{"begin":645,"end":650},"obj":"CD"},{"id":"T27058","span":{"begin":642,"end":644},"obj":"IN"},{"id":"T27057","span":{"begin":626,"end":641},"obj":"NN"},{"id":"T27056","span":{"begin":617,"end":625},"obj":"NN"},{"id":"T27055","span":{"begin":603,"end":616},"obj":"JJ"},{"id":"T27054","span":{"begin":601,"end":602},"obj":","},{"id":"T27053","span":{"begin":591,"end":601},"obj":"NN"},{"id":"T27052","span":{"begin":585,"end":590},"obj":"CD"},{"id":"T27051","span":{"begin":572,"end":584},"obj":"JJ"},{"id":"T27050","span":{"begin":568,"end":571},"obj":"CC"},{"id":"T27049","span":{"begin":557,"end":567},"obj":"NN"},{"id":"T27048","span":{"begin":549,"end":556},"obj":"NN"},{"id":"T27047","span":{"begin":538,"end":548},"obj":"JJ"},{"id":"T27046","span":{"begin":530,"end":537},"obj":"IN"},{"id":"T27045","span":{"begin":528,"end":529},"obj":"."},{"id":"T27044","span":{"begin":523,"end":528},"obj":"NNS"},{"id":"T27043","span":{"begin":521,"end":522},"obj":"NNP"},{"id":"T27042","span":{"begin":519,"end":520},"obj":"CD"},{"id":"T27041","span":{"begin":516,"end":519},"obj":"NNP"},{"id":"T27040","span":{"begin":509,"end":515},"obj":"JJ"},{"id":"T27039","span":{"begin":504,"end":508},"obj":"IN"},{"id":"T27038","span":{"begin":490,"end":503},"obj":"NN"},{"id":"T27037","span":{"begin":485,"end":489},"obj":"NNP"},{"id":"T27036","span":{"begin":481,"end":484},"obj":"CC"},{"id":"T27035","span":{"begin":477,"end":480},"obj":"NNP"},{"id":"T27034","span":{"begin":471,"end":476},"obj":"IN"},{"id":"T27033","span":{"begin":465,"end":470},"obj":"JJ"},{"id":"T27032","span":{"begin":462,"end":464},"obj":"IN"},{"id":"T27031","span":{"begin":455,"end":461},"obj":"NNS"},{"id":"T27030","span":{"begin":448,"end":454},"obj":"JJR"},{"id":"T27029","span":{"begin":440,"end":447},"obj":"VB"},{"id":"T27028","span":{"begin":437,"end":439},"obj":"TO"},{"id":"T27027","span":{"begin":432,"end":436},"obj":"JJ"},{"id":"T27026","span":{"begin":428,"end":431},"obj":"VBP"},{"id":"T27025","span":{"begin":426,"end":427},"obj":","},{"id":"T27024","span":{"begin":421,"end":426},"obj":"NNP"},{"id":"T27023","span":{"begin":418,"end":420},"obj":"IN"},{"id":"T27022","span":{"begin":409,"end":417},"obj":"NN"},{"id":"T27021","span":{"begin":405,"end":408},"obj":"DT"},{"id":"T27020","span":{"begin":402,"end":404},"obj":"IN"},{"id":"T27019","span":{"begin":400,"end":401},"obj":","},{"id":"T27018","span":{"begin":398,"end":400},"obj":"NNP"},{"id":"T27017","span":{"begin":391,"end":397},"obj":"JJ"},{"id":"T27016","span":{"begin":386,"end":390},"obj":"IN"},{"id":"T27015","span":{"begin":377,"end":385},"obj":"NNS"},{"id":"T27014","span":{"begin":372,"end":376},"obj":"IN"},{"id":"T27013","span":{"begin":366,"end":371},"obj":"NNS"},{"id":"T27012","span":{"begin":364,"end":365},"obj":"NNP"},{"id":"T27011","span":{"begin":362,"end":363},"obj":"VBD"},{"id":"T27010","span":{"begin":359,"end":362},"obj":"NNP"},{"id":"T27009","span":{"begin":356,"end":358},"obj":"NNP"},{"id":"T26948","span":{"begin":12,"end":13},"obj":"DT"},{"id":"T26947","span":{"begin":6,"end":11},"obj":"VBZ"},{"id":"T26946","span":{"begin":0,"end":5},"obj":"NN"},{"id":"T26972","span":{"begin":149,"end":157},"obj":"VBZ"},{"id":"T26971","span":{"begin":143,"end":148},"obj":"NN"},{"id":"T26970","span":{"begin":141,"end":142},"obj":"."},{"id":"T26969","span":{"begin":140,"end":141},"obj":"NNP"},{"id":"T26968","span":{"begin":139,"end":140},"obj":"CD"},{"id":"T26967","span":{"begin":138,"end":139},"obj":"VBP"},{"id":"T26966","span":{"begin":132,"end":137},"obj":"NNS"},{"id":"T26965","span":{"begin":128,"end":131},"obj":"JJ"},{"id":"T26964","span":{"begin":124,"end":127},"obj":"CC"},{"id":"T26963","span":{"begin":112,"end":123},"obj":"NNS"},{"id":"T26962","span":{"begin":107,"end":111},"obj":"DT"},{"id":"T26961","span":{"begin":104,"end":106},"obj":"IN"},{"id":"T26960","span":{"begin":95,"end":103},"obj":"NN"},{"id":"T26959","span":{"begin":91,"end":94},"obj":"DT"},{"id":"T26958","span":{"begin":80,"end":90},"obj":"VBG"},{"id":"T26957","span":{"begin":77,"end":79},"obj":"IN"},{"id":"T26956","span":{"begin":67,"end":76},"obj":"NNS"},{"id":"T26955","span":{"begin":54,"end":66},"obj":"JJ"},{"id":"T26954","span":{"begin":50,"end":53},"obj":"CC"},{"id":"T26953","span":{"begin":43,"end":49},"obj":"JJ"},{"id":"T26952","span":{"begin":34,"end":42},"obj":"VBG"},{"id":"T26951","span":{"begin":31,"end":33},"obj":"IN"},{"id":"T26950","span":{"begin":26,"end":30},"obj":"NN"},{"id":"T26949","span":{"begin":14,"end":25},"obj":"JJ"},{"id":"T26991","span":{"begin":281,"end":288},"obj":"RB"},{"id":"T26990","span":{"begin":277,"end":280},"obj":"CC"},{"id":"T26989","span":{"begin":275,"end":276},"obj":","},{"id":"T26988","span":{"begin":270,"end":275},"obj":"NNS"},{"id":"T26987","span":{"begin":268,"end":269},"obj":"NNP"},{"id":"T26986","span":{"begin":265,"end":267},"obj":"IN"},{"id":"T26985","span":{"begin":257,"end":264},"obj":"JJ"},{"id":"T26984","span":{"begin":248,"end":256},"obj":"JJ"},{"id":"T26983","span":{"begin":227,"end":247},"obj":"NN"},{"id":"T26982","span":{"begin":216,"end":226},"obj":"JJ"},{"id":"T26981","span":{"begin":212,"end":215},"obj":"DT"},{"id":"T26980","span":{"begin":208,"end":211},"obj":"CC"},{"id":"T26979","span":{"begin":199,"end":207},"obj":"NN"},{"id":"T26978","span":{"begin":194,"end":198},"obj":"NNP"},{"id":"T26977","span":{"begin":190,"end":193},"obj":"DT"},{"id":"T26976","span":{"begin":187,"end":189},"obj":"IN"},{"id":"T26975","span":{"begin":171,"end":186},"obj":"NN"},{"id":"T26974","span":{"begin":162,"end":170},"obj":"NN"},{"id":"T26973","span":{"begin":158,"end":161},"obj":"DT"},{"id":"T27008","span":{"begin":351,"end":355},"obj":"IN"},{"id":"T27007","span":{"begin":345,"end":350},"obj":"VBD"},{"id":"T27006","span":{"begin":342,"end":344},"obj":"PRP"},{"id":"T27005","span":{"begin":340,"end":341},"obj":","},{"id":"T27004","span":{"begin":335,"end":340},"obj":"NN"},{"id":"T27003","span":{"begin":327,"end":334},"obj":"JJ"},{"id":"T27002","span":{"begin":323,"end":326},"obj":"DT"},{"id":"T27001","span":{"begin":320,"end":322},"obj":"IN"},{"id":"T27000","span":{"begin":318,"end":319},"obj":"."},{"id":"T26999","span":{"begin":317,"end":318},"obj":"NNP"},{"id":"T26998","span":{"begin":315,"end":317},"obj":"CD"},{"id":"T26997","span":{"begin":314,"end":315},"obj":"NNP"},{"id":"T26996","span":{"begin":308,"end":313},"obj":"NNS"},{"id":"T26995","span":{"begin":306,"end":307},"obj":"NNP"},{"id":"T26994","span":{"begin":303,"end":305},"obj":"IN"},{"id":"T26993","span":{"begin":298,"end":302},"obj":"VBZ"},{"id":"T26992","span":{"begin":289,"end":297},"obj":"RB"},{"id":"T27087","span":{"begin":789,"end":794},"obj":"NNP"},{"id":"T27086","span":{"begin":787,"end":788},"obj":"."},{"id":"T27085","span":{"begin":782,"end":787},"obj":"NNP"},{"id":"T27084","span":{"begin":779,"end":781},"obj":"IN"},{"id":"T27083","span":{"begin":769,"end":778},"obj":"JJ"},{"id":"T27082","span":{"begin":752,"end":768},"obj":"RB"},{"id":"T27081","span":{"begin":749,"end":751},"obj":"VBZ"},{"id":"T27080","span":{"begin":733,"end":748},"obj":"NN"},{"id":"T27079","span":{"begin":727,"end":732},"obj":"NNP"},{"id":"T27078","span":{"begin":721,"end":726},"obj":"WRB"},{"id":"T27077","span":{"begin":719,"end":720},"obj":","},{"id":"T27076","span":{"begin":714,"end":719},"obj":"NNS"},{"id":"T27075","span":{"begin":712,"end":713},"obj":"NNP"},{"id":"T27074","span":{"begin":710,"end":711},"obj":"CD"},{"id":"T27073","span":{"begin":707,"end":710},"obj":"NNP"},{"id":"T27183","span":{"begin":1347,"end":1351},"obj":"IN"},{"id":"T27182","span":{"begin":1335,"end":1346},"obj":"NN"},{"id":"T27190","span":{"begin":1403,"end":1404},"obj":"."},{"id":"T27189","span":{"begin":1394,"end":1403},"obj":"NN"},{"id":"T27188","span":{"begin":1388,"end":1393},"obj":"CD"},{"id":"T27187","span":{"begin":1384,"end":1387},"obj":"CC"}],"relations":[{"id":"R13713","pred":"nsubj","subj":"T26946","obj":"T26947"},{"id":"R13714","pred":"ROOT","subj":"T26947","obj":"T26947"},{"id":"R13716","pred":"det","subj":"T26948","obj":"T26950"},{"id":"R13717","pred":"amod","subj":"T26949","obj":"T26950"},{"id":"R13718","pred":"dobj","subj":"T26950","obj":"T26947"},{"id":"R13719","pred":"prep","subj":"T26951","obj":"T26950"},{"id":"R13720","pred":"pcomp","subj":"T26952","obj":"T26951"},{"id":"R13721","pred":"amod","subj":"T26953","obj":"T26956"},{"id":"R13723","pred":"cc","subj":"T26954","obj":"T26953"},{"id":"R13724","pred":"conj","subj":"T26955","obj":"T26953"},{"id":"R13725","pred":"dobj","subj":"T26956","obj":"T26952"},{"id":"R13727","pred":"prep","subj":"T26957","obj":"T26952"},{"id":"R13728","pred":"pcomp","subj":"T26958","obj":"T26957"},{"id":"R13729","pred":"det","subj":"T26959","obj":"T26960"},{"id":"R13731","pred":"dobj","subj":"T26960","obj":"T26958"},{"id":"R13732","pred":"prep","subj":"T26961","obj":"T26960"},{"id":"R13733","pred":"det","subj":"T26962","obj":"T26963"},{"id":"R13735","pred":"pobj","subj":"T26963","obj":"T26961"},{"id":"R13736","pred":"cc","subj":"T26964","obj":"T26963"},{"id":"R13737","pred":"amod","subj":"T26965","obj":"T26966"},{"id":"R13739","pred":"conj","subj":"T26966","obj":"T26963"},{"id":"R13740","pred":"conj","subj":"T26967","obj":"T26947"},{"id":"R13741","pred":"nummod","subj":"T26968","obj":"T26969"},{"id":"R13743","pred":"dobj","subj":"T26969","obj":"T26967"},{"id":"R13744","pred":"punct","subj":"T26970","obj":"T26947"},{"id":"R13745","pred":"nsubj","subj":"T26971","obj":"T26972"},{"id":"R13747","pred":"ROOT","subj":"T26972","obj":"T26972"},{"id":"R13750","pred":"det","subj":"T26973","obj":"T26975"},{"id":"R13752","pred":"compound","subj":"T26974","obj":"T26975"},{"id":"R13753","pred":"dobj","subj":"T26975","obj":"T26972"},{"id":"R13754","pred":"prep","subj":"T26976","obj":"T26975"},{"id":"R13756","pred":"det","subj":"T26977","obj":"T26979"},{"id":"R13757","pred":"compound","subj":"T26978","obj":"T26979"},{"id":"R13758","pred":"pobj","subj":"T26979","obj":"T26976"},{"id":"R13760","pred":"cc","subj":"T26980","obj":"T26975"},{"id":"R13761","pred":"det","subj":"T26981","obj":"T26985"},{"id":"R13762","pred":"amod","subj":"T26982","obj":"T26985"},{"id":"R13764","pred":"advmod","subj":"T26983","obj":"T26985"},{"id":"R13765","pred":"advmod","subj":"T26984","obj":"T26985"},{"id":"R13766","pred":"conj","subj":"T26985","obj":"T26975"},{"id":"R13768","pred":"prep","subj":"T26986","obj":"T26985"},{"id":"R13769","pred":"compound","subj":"T26987","obj":"T26988"},{"id":"R13770","pred":"pobj","subj":"T26988","obj":"T26986"},{"id":"R13771","pred":"punct","subj":"T26989","obj":"T26985"},{"id":"R13772","pred":"cc","subj":"T26990","obj":"T26985"},{"id":"R13773","pred":"advmod","subj":"T26991","obj":"T26993"},{"id":"R13778","pred":"advmod","subj":"T26992","obj":"T26993"},{"id":"R13779","pred":"conj","subj":"T26993","obj":"T26972"},{"id":"R13780","pred":"prep","subj":"T26994","obj":"T26993"},{"id":"R13782","pred":"compound","subj":"T26995","obj":"T26996"},{"id":"R13783","pred":"pobj","subj":"T26996","obj":"T26994"},{"id":"R13785","pred":"nmod","subj":"T26997","obj":"T26999"},{"id":"R13786","pred":"nummod","subj":"T26998","obj":"T26999"},{"id":"R13787","pred":"appos","subj":"T26999","obj":"T26996"},{"id":"R13788","pred":"punct","subj":"T27000","obj":"T26972"},{"id":"R13790","pred":"prep","subj":"T27001","obj":"T27007"},{"id":"R13791","pred":"det","subj":"T27002","obj":"T27004"},{"id":"R13793","pred":"amod","subj":"T27003","obj":"T27004"},{"id":"R13794","pred":"pobj","subj":"T27004","obj":"T27001"},{"id":"R13795","pred":"punct","subj":"T27005","obj":"T27007"},{"id":"R13797","pred":"nsubj","subj":"T27006","obj":"T27007"},{"id":"R13798","pred":"ROOT","subj":"T27007","obj":"T27007"},{"id":"R13799","pred":"mark","subj":"T27008","obj":"T27011"},{"id":"R13801","pred":"compound","subj":"T27009","obj":"T27010"},{"id":"R13802","pred":"nsubj","subj":"T27010","obj":"T27011"},{"id":"R13804","pred":"advcl","subj":"T27011","obj":"T27026"},{"id":"R13805","pred":"compound","subj":"T27012","obj":"T27013"},{"id":"R13806","pred":"dobj","subj":"T27013","obj":"T27011"},{"id":"R13807","pred":"prep","subj":"T27014","obj":"T27011"},{"id":"R13809","pred":"pobj","subj":"T27015","obj":"T27014"},{"id":"R13810","pred":"prep","subj":"T27016","obj":"T27015"},{"id":"R13813","pred":"amod","subj":"T27017","obj":"T27018"},{"id":"R13814","pred":"pobj","subj":"T27018","obj":"T27016"},{"id":"R13816","pred":"punct","subj":"T27019","obj":"T27026"},{"id":"R13817","pred":"prep","subj":"T27020","obj":"T27026"},{"id":"R13818","pred":"det","subj":"T27021","obj":"T27022"},{"id":"R13819","pred":"pobj","subj":"T27022","obj":"T27020"},{"id":"R13820","pred":"prep","subj":"T27023","obj":"T27022"},{"id":"R13821","pred":"pobj","subj":"T27024","obj":"T27023"},{"id":"R13823","pred":"punct","subj":"T27025","obj":"T27026"},{"id":"R13824","pred":"ccomp","subj":"T27026","obj":"T27007"},{"id":"R13826","pred":"acomp","subj":"T27027","obj":"T27026"},{"id":"R13827","pred":"aux","subj":"T27028","obj":"T27029"},{"id":"R13828","pred":"xcomp","subj":"T27029","obj":"T27027"},{"id":"R13829","pred":"amod","subj":"T27030","obj":"T27031"},{"id":"R13831","pred":"dobj","subj":"T27031","obj":"T27029"},{"id":"R13832","pred":"prep","subj":"T27032","obj":"T27031"},{"id":"R13833","pred":"pobj","subj":"T27033","obj":"T27032"},{"id":"R13835","pred":"prep","subj":"T27034","obj":"T27029"},{"id":"R13836","pred":"pobj","subj":"T27035","obj":"T27034"},{"id":"R13838","pred":"cc","subj":"T27036","obj":"T27035"},{"id":"R13839","pred":"compound","subj":"T27037","obj":"T27038"},{"id":"R13840","pred":"conj","subj":"T27038","obj":"T27035"},{"id":"R13842","pred":"prep","subj":"T27039","obj":"T27038"},{"id":"R13843","pred":"amod","subj":"T27040","obj":"T27044"},{"id":"R13845","pred":"compound","subj":"T27041","obj":"T27044"},{"id":"R13846","pred":"nummod","subj":"T27042","obj":"T27044"},{"id":"R13847","pred":"compound","subj":"T27043","obj":"T27044"},{"id":"R13848","pred":"pobj","subj":"T27044","obj":"T27039"},{"id":"R13849","pred":"compound","subj":"T27073","obj":"T27076"},{"id":"R13850","pred":"punct","subj":"T27045","obj":"T27007"},{"id":"R13851","pred":"prep","subj":"T27046","obj":"T27061"},{"id":"R13852","pred":"amod","subj":"T27047","obj":"T27049"},{"id":"R13853","pred":"nummod","subj":"T27074","obj":"T27076"},{"id":"R13854","pred":"compound","subj":"T27048","obj":"T27049"},{"id":"R13855","pred":"pobj","subj":"T27049","obj":"T27046"},{"id":"R13856","pred":"cc","subj":"T27050","obj":"T27049"},{"id":"R13857","pred":"compound","subj":"T27075","obj":"T27076"},{"id":"R13858","pred":"amod","subj":"T27051","obj":"T27053"},{"id":"R13859","pred":"nummod","subj":"T27052","obj":"T27053"},{"id":"R13860","pred":"conj","subj":"T27053","obj":"T27049"},{"id":"R13861","pred":"pobj","subj":"T27076","obj":"T27071"},{"id":"R13862","pred":"punct","subj":"T27054","obj":"T27053"},{"id":"R13863","pred":"nmod","subj":"T27055","obj":"T27057"},{"id":"R13864","pred":"compound","subj":"T27056","obj":"T27057"},{"id":"R13865","pred":"punct","subj":"T27077","obj":"T27076"},{"id":"R13866","pred":"conj","subj":"T27057","obj":"T27053"},{"id":"R13867","pred":"prep","subj":"T27058","obj":"T27057"},{"id":"R13868","pred":"pobj","subj":"T27059","obj":"T27058"},{"id":"R13869","pred":"auxpass","subj":"T27060","obj":"T27061"},{"id":"R13870","pred":"ROOT","subj":"T27061","obj":"T27061"},{"id":"R13871","pred":"prep","subj":"T27062","obj":"T27061"},{"id":"R13872","pred":"compound","subj":"T27063","obj":"T27064"},{"id":"R13873","pred":"advmod","subj":"T27078","obj":"T27081"},{"id":"R13874","pred":"pobj","subj":"T27064","obj":"T27062"},{"id":"R13875","pred":"amod","subj":"T27065","obj":"T27067"},{"id":"R13876","pred":"compound","subj":"T27066","obj":"T27067"},{"id":"R13877","pred":"compound","subj":"T27079","obj":"T27080"},{"id":"R13878","pred":"dobj","subj":"T27067","obj":"T27061"},{"id":"R13879","pred":"punct","subj":"T27068","obj":"T27061"},{"id":"R13880","pred":"prep","subj":"T27069","obj":"T27061"},{"id":"R13881","pred":"nsubj","subj":"T27080","obj":"T27081"},{"id":"R13882","pred":"pobj","subj":"T27070","obj":"T27069"},{"id":"R13883","pred":"prep","subj":"T27071","obj":"T27070"},{"id":"R13884","pred":"amod","subj":"T27072","obj":"T27076"},{"id":"R13885","pred":"relcl","subj":"T27081","obj":"T27076"},{"id":"R13886","pred":"advmod","subj":"T27082","obj":"T27083"},{"id":"R13887","pred":"acomp","subj":"T27083","obj":"T27081"},{"id":"R13888","pred":"prep","subj":"T27084","obj":"T27083"},{"id":"R13889","pred":"nsubj","subj":"T27088","obj":"T27092"},{"id":"R13890","pred":"prep","subj":"T27089","obj":"T27088"},{"id":"R13891","pred":"pobj","subj":"T27085","obj":"T27084"},{"id":"R13892","pred":"compound","subj":"T27090","obj":"T27091"},{"id":"R13893","pred":"pobj","subj":"T27091","obj":"T27089"},{"id":"R13894","pred":"ROOT","subj":"T27092","obj":"T27092"},{"id":"R13895","pred":"punct","subj":"T27086","obj":"T27061"},{"id":"R13896","pred":"dobj","subj":"T27093","obj":"T27092"},{"id":"R13897","pred":"cc","subj":"T27094","obj":"T27093"},{"id":"R13898","pred":"neg","subj":"T27095","obj":"T27097"},{"id":"R13899","pred":"compound","subj":"T27087","obj":"T27088"},{"id":"R13954","pred":"pobj","subj":"T27134","obj":"T27132"},{"id":"R13955","pred":"prep","subj":"T27135","obj":"T27129"},{"id":"R13957","pred":"pobj","subj":"T27136","obj":"T27135"},{"id":"R13958","pred":"prep","subj":"T27137","obj":"T27136"},{"id":"R13959","pred":"amod","subj":"T27138","obj":"T27142"},{"id":"R13961","pred":"compound","subj":"T27139","obj":"T27142"},{"id":"R13962","pred":"nummod","subj":"T27140","obj":"T27142"},{"id":"R13964","pred":"compound","subj":"T27141","obj":"T27142"},{"id":"R13965","pred":"pobj","subj":"T27142","obj":"T27137"},{"id":"R13966","pred":"punct","subj":"T27143","obj":"T27123"},{"id":"R13968","pred":"det","subj":"T27144","obj":"T27145"},{"id":"R13969","pred":"nsubj","subj":"T27145","obj":"T27146"},{"id":"R13970","pred":"ROOT","subj":"T27146","obj":"T27146"},{"id":"R13971","pred":"mark","subj":"T27147","obj":"T27152"},{"id":"R13972","pred":"nsubj","subj":"T27148","obj":"T27152"},{"id":"R13974","pred":"nummod","subj":"T27149","obj":"T27151"},{"id":"R13975","pred":"compound","subj":"T27150","obj":"T27151"},{"id":"R13976","pred":"nsubj","subj":"T27151","obj":"T27152"},{"id":"R13977","pred":"ccomp","subj":"T27152","obj":"T27146"},{"id":"R13979","pred":"acomp","subj":"T27153","obj":"T27152"},{"id":"R13980","pred":"prep","subj":"T27154","obj":"T27153"},{"id":"R13981","pred":"det","subj":"T27155","obj":"T27157"},{"id":"R13983","pred":"amod","subj":"T27156","obj":"T27157"},{"id":"R13984","pred":"pobj","subj":"T27157","obj":"T27154"},{"id":"R13985","pred":"prep","subj":"T27158","obj":"T27157"},{"id":"R13987","pred":"pobj","subj":"T27159","obj":"T27158"},{"id":"R13988","pred":"prep","subj":"T27160","obj":"T27152"},{"id":"R13989","pred":"pobj","subj":"T27161","obj":"T27160"},{"id":"R13991","pred":"prep","subj":"T27162","obj":"T27161"},{"id":"R13992","pred":"det","subj":"T27163","obj":"T27165"},{"id":"R13993","pred":"amod","subj":"T27164","obj":"T27165"},{"id":"R13995","pred":"pobj","subj":"T27165","obj":"T27162"},{"id":"R13996","pred":"punct","subj":"T27166","obj":"T27152"},{"id":"R13997","pred":"cc","subj":"T27167","obj":"T27152"},{"id":"R13999","pred":"conj","subj":"T27168","obj":"T27152"},{"id":"R14000","pred":"mark","subj":"T27169","obj":"T27173"},{"id":"R14002","pred":"det","subj":"T27170","obj":"T27171"},{"id":"R14003","pred":"nsubj","subj":"T27171","obj":"T27173"},{"id":"R14004","pred":"aux","subj":"T27172","obj":"T27173"},{"id":"R14005","pred":"ccomp","subj":"T27173","obj":"T27168"},{"id":"R14007","pred":"acomp","subj":"T27174","obj":"T27173"},{"id":"R14008","pred":"prep","subj":"T27175","obj":"T27174"},{"id":"R14009","pred":"amod","subj":"T27176","obj":"T27179"},{"id":"R14011","pred":"amod","subj":"T27177","obj":"T27179"},{"id":"R14012","pred":"nummod","subj":"T27178","obj":"T27179"},{"id":"R14014","pred":"pobj","subj":"T27179","obj":"T27175"},{"id":"R14015","pred":"punct","subj":"T27180","obj":"T27173"},{"id":"R14016","pred":"prep","subj":"T27181","obj":"T27173"},{"id":"R13901","pred":"nummod","subj":"T27096","obj":"T27097"},{"id":"R13902","pred":"nsubj","subj":"T27097","obj":"T27108"},{"id":"R13904","pred":"prep","subj":"T27098","obj":"T27097"},{"id":"R13905","pred":"amod","subj":"T27099","obj":"T27103"},{"id":"R13906","pred":"compound","subj":"T27100","obj":"T27103"},{"id":"R13907","pred":"nummod","subj":"T27101","obj":"T27103"},{"id":"R13910","pred":"compound","subj":"T27102","obj":"T27103"},{"id":"R13912","pred":"pobj","subj":"T27103","obj":"T27098"},{"id":"R13914","pred":"punct","subj":"T27104","obj":"T27097"},{"id":"R13915","pred":"cc","subj":"T27105","obj":"T27097"},{"id":"R13916","pred":"amod","subj":"T27106","obj":"T27107"},{"id":"R13917","pred":"conj","subj":"T27107","obj":"T27097"},{"id":"R13919","pred":"conj","subj":"T27108","obj":"T27092"},{"id":"R13920","pred":"det","subj":"T27109","obj":"T27110"},{"id":"R13921","pred":"dobj","subj":"T27110","obj":"T27108"},{"id":"R13922","pred":"prep","subj":"T27111","obj":"T27110"},{"id":"R13923","pred":"compound","subj":"T27112","obj":"T27113"},{"id":"R13924","pred":"pobj","subj":"T27113","obj":"T27111"},{"id":"R13926","pred":"prep","subj":"T27114","obj":"T27113"},{"id":"R13927","pred":"amod","subj":"T27115","obj":"T27116"},{"id":"R13928","pred":"pobj","subj":"T27116","obj":"T27114"},{"id":"R13930","pred":"punct","subj":"T27117","obj":"T27108"},{"id":"R13931","pred":"compound","subj":"T27118","obj":"T27119"},{"id":"R13932","pred":"compound","subj":"T27119","obj":"T27122"},{"id":"R13934","pred":"amod","subj":"T27120","obj":"T27122"},{"id":"R13935","pred":"compound","subj":"T27121","obj":"T27122"},{"id":"R13937","pred":"nsubj","subj":"T27122","obj":"T27123"},{"id":"R13938","pred":"ROOT","subj":"T27123","obj":"T27123"},{"id":"R13939","pred":"amod","subj":"T27124","obj":"T27125"},{"id":"R13941","pred":"dobj","subj":"T27125","obj":"T27123"},{"id":"R13942","pred":"prep","subj":"T27126","obj":"T27125"},{"id":"R13943","pred":"pobj","subj":"T27127","obj":"T27126"},{"id":"R13945","pred":"cc","subj":"T27128","obj":"T27123"},{"id":"R13946","pred":"conj","subj":"T27129","obj":"T27123"},{"id":"R13947","pred":"amod","subj":"T27130","obj":"T27131"},{"id":"R13949","pred":"dobj","subj":"T27131","obj":"T27129"},{"id":"R13950","pred":"prep","subj":"T27132","obj":"T27131"},{"id":"R13951","pred":"nummod","subj":"T27133","obj":"T27134"},{"id":"R13900","pred":"pobj","subj":"T27182","obj":"T27181"},{"id":"R13903","pred":"prep","subj":"T27183","obj":"T27182"},{"id":"R13908","pred":"amod","subj":"T27184","obj":"T27186"},{"id":"R13909","pred":"compound","subj":"T27185","obj":"T27186"},{"id":"R13911","pred":"pobj","subj":"T27186","obj":"T27183"},{"id":"R13913","pred":"cc","subj":"T27187","obj":"T27186"},{"id":"R13918","pred":"nummod","subj":"T27188","obj":"T27189"},{"id":"R13925","pred":"conj","subj":"T27189","obj":"T27186"},{"id":"R13929","pred":"punct","subj":"T27190","obj":"T27146"}],"text":"IL-10 plays a predominant role in limiting immune and inflammatory responses by regulating the function of both macrophages and Th1 cells [1]. IL-10 inhibits the tyrosine phosphorylation of the CD28 molecule and the subsequent phosphatidylinositol 3-kinase binding in T cells, and thereby directly acts on T cells [24]. In the present study, we found that PB CD4+ T cells from patients with active RA, in the presence of IL-10, are able to produce higher levels of IFN-γ after CD3 and CD28 costimulation than normal CD4+ T cells. Despite high-level IL-10R1 expression and constitutive STAT3 activation, IL-10-induced tyrosine phosphorylation of STAT3 is suppressed in RA CD4+ T cells, in contrast to normal CD4+ T cells, where STAT3 phosphorylation is dose-dependently inducible by IL-10. Serum IL-6 from RA patients induces STAT3 but not STAT1 phosphorylation in normal CD4+ T cells, and exogenous IL-6 induces the resistance to IL-10 inhibition of IFN-γ production. RA CD4+ T cells contain higher levels of SOCS1 but contain lower levels of SOCS3 transcripts in comparison with normal CD4+ T cells. These findings indicate that CD4+ T cells become resistant to the inhibitory effect of IL-10 before migration into the inflamed ST, and suggest that this resistance may be attributable to impaired IL-10-dependent STAT3 activation, in association with sustained STAT3 phosphorylation and SOCS1 induction."}
bionlp-st-ge-2016-test-tees
{"project":"bionlp-st-ge-2016-test-tees","denotations":[{"id":"T23973","span":{"begin":1394,"end":1403},"obj":"Positive_regulation"},{"id":"T23972","span":{"begin":1394,"end":1403},"obj":"Positive_regulation"},{"id":"T23971","span":{"begin":1368,"end":1383},"obj":"Phosphorylation"},{"id":"T23970","span":{"begin":1388,"end":1393},"obj":"Protein"},{"id":"T23969","span":{"begin":1362,"end":1367},"obj":"Protein"},{"id":"T23968","span":{"begin":1314,"end":1319},"obj":"Protein"},{"id":"T23967","span":{"begin":1298,"end":1303},"obj":"Protein"},{"id":"T23966","span":{"begin":1130,"end":1134},"obj":"Protein"},{"id":"T23965","span":{"begin":1033,"end":1039},"obj":"Positive_regulation"},{"id":"T23964","span":{"begin":999,"end":1005},"obj":"Positive_regulation"},{"id":"T23963","span":{"begin":1087,"end":1091},"obj":"Protein"},{"id":"T23962","span":{"begin":1043,"end":1060},"obj":"Protein"},{"id":"T23961","span":{"begin":1009,"end":1014},"obj":"Protein"},{"id":"T23960","span":{"begin":971,"end":975},"obj":"Protein"},{"id":"T23959","span":{"begin":904,"end":911},"obj":"Positive_regulation"},{"id":"T23958","span":{"begin":916,"end":926},"obj":"Positive_regulation"},{"id":"T23957","span":{"begin":936,"end":946},"obj":"Negative_regulation"},{"id":"T23956","span":{"begin":817,"end":824},"obj":"Positive_regulation"},{"id":"T23955","span":{"begin":817,"end":824},"obj":"Positive_regulation"},{"id":"T23954","span":{"begin":956,"end":966},"obj":"Gene_expression"},{"id":"T23953","span":{"begin":845,"end":860},"obj":"Phosphorylation"},{"id":"T23952","span":{"begin":845,"end":860},"obj":"Phosphorylation"},{"id":"T23951","span":{"begin":950,"end":955},"obj":"Protein"},{"id":"T23950","span":{"begin":930,"end":935},"obj":"Protein"},{"id":"T23949","span":{"begin":899,"end":903},"obj":"Protein"},{"id":"T23948","span":{"begin":871,"end":875},"obj":"Protein"},{"id":"T23947","span":{"begin":839,"end":844},"obj":"Protein"},{"id":"T23946","span":{"begin":825,"end":830},"obj":"Protein"},{"id":"T23945","span":{"begin":538,"end":548},"obj":"Positive_regulation"},{"id":"T23944","span":{"begin":769,"end":778},"obj":"Positive_regulation"},{"id":"T23943","span":{"begin":733,"end":748},"obj":"Phosphorylation"},{"id":"T23942","span":{"begin":654,"end":664},"obj":"Negative_regulation"},{"id":"T23941","span":{"begin":626,"end":641},"obj":"Phosphorylation"},{"id":"T23940","span":{"begin":617,"end":625},"obj":"Entity"},{"id":"T23939","span":{"begin":591,"end":601},"obj":"Positive_regulation"},{"id":"T23938","span":{"begin":557,"end":567},"obj":"Gene_expression"},{"id":"T23937","span":{"begin":782,"end":787},"obj":"Protein"},{"id":"T23936","span":{"begin":727,"end":732},"obj":"Protein"},{"id":"T23935","span":{"begin":707,"end":710},"obj":"Protein"},{"id":"T23934","span":{"begin":668,"end":674},"obj":"Protein"},{"id":"T23933","span":{"begin":645,"end":650},"obj":"Protein"},{"id":"T23932","span":{"begin":585,"end":590},"obj":"Protein"},{"id":"T23931","span":{"begin":549,"end":556},"obj":"Protein"},{"id":"T23930","span":{"begin":440,"end":447},"obj":"Gene_expression"},{"id":"T23929","span":{"begin":440,"end":447},"obj":"Gene_expression"},{"id":"T23928","span":{"begin":516,"end":520},"obj":"Protein"},{"id":"T23927","span":{"begin":485,"end":489},"obj":"Protein"},{"id":"T23926","span":{"begin":477,"end":480},"obj":"Protein"},{"id":"T23925","span":{"begin":465,"end":470},"obj":"Protein"},{"id":"T23920","span":{"begin":162,"end":170},"obj":"Entity"},{"id":"T23919","span":{"begin":194,"end":207},"obj":"Protein"},{"id":"T23918","span":{"begin":143,"end":148},"obj":"Protein"},{"id":"T23924","span":{"begin":421,"end":426},"obj":"Protein"},{"id":"T23923","span":{"begin":359,"end":362},"obj":"Protein"},{"id":"T23922","span":{"begin":149,"end":157},"obj":"Negative_regulation"},{"id":"T23921","span":{"begin":171,"end":186},"obj":"Phosphorylation"}],"relations":[{"id":"R11428","pred":"themeOf","subj":"T23961","obj":"T23964"},{"id":"R11429","pred":"themeOf","subj":"T23962","obj":"T23965"},{"id":"R11430","pred":"themeOf","subj":"T23969","obj":"T23971"},{"id":"R11402","pred":"causeOf","subj":"T23918","obj":"T23922"},{"id":"R11403","pred":"themeOf","subj":"T23919","obj":"T23921"},{"id":"R11404","pred":"partOf","subj":"T23919","obj":"T23920"},{"id":"R11405","pred":"Site","subj":"T23920","obj":"T23921"},{"id":"R11406","pred":"themeOf","subj":"T23921","obj":"T23922"},{"id":"R11407","pred":"themeOf","subj":"T23925","obj":"T23929"},{"id":"R11408","pred":"themeOf","subj":"T23926","obj":"T23930"},{"id":"R11409","pred":"themeOf","subj":"T23931","obj":"T23938"},{"id":"R11410","pred":"themeOf","subj":"T23932","obj":"T23939"},{"id":"R11411","pred":"themeOf","subj":"T23933","obj":"T23941"},{"id":"R11412","pred":"partOf","subj":"T23933","obj":"T23940"},{"id":"R11413","pred":"themeOf","subj":"T23936","obj":"T23943"},{"id":"R11414","pred":"causeOf","subj":"T23937","obj":"T23944"},{"id":"R11415","pred":"themeOf","subj":"T23938","obj":"T23945"},{"id":"R11416","pred":"Site","subj":"T23940","obj":"T23941"},{"id":"R11417","pred":"themeOf","subj":"T23941","obj":"T23942"},{"id":"R11418","pred":"themeOf","subj":"T23943","obj":"T23944"},{"id":"R11419","pred":"themeOf","subj":"T23946","obj":"T23952"},{"id":"R11420","pred":"themeOf","subj":"T23947","obj":"T23953"},{"id":"R11421","pred":"causeOf","subj":"T23949","obj":"T23959"},{"id":"R11422","pred":"themeOf","subj":"T23951","obj":"T23954"},{"id":"R11423","pred":"themeOf","subj":"T23952","obj":"T23955"},{"id":"R11424","pred":"themeOf","subj":"T23953","obj":"T23956"},{"id":"R11425","pred":"themeOf","subj":"T23954","obj":"T23957"},{"id":"R11426","pred":"themeOf","subj":"T23957","obj":"T23958"},{"id":"R11427","pred":"themeOf","subj":"T23958","obj":"T23959"},{"id":"R11431","pred":"themeOf","subj":"T23970","obj":"T23972"},{"id":"R11432","pred":"themeOf","subj":"T23971","obj":"T23973"}],"text":"IL-10 plays a predominant role in limiting immune and inflammatory responses by regulating the function of both macrophages and Th1 cells [1]. IL-10 inhibits the tyrosine phosphorylation of the CD28 molecule and the subsequent phosphatidylinositol 3-kinase binding in T cells, and thereby directly acts on T cells [24]. In the present study, we found that PB CD4+ T cells from patients with active RA, in the presence of IL-10, are able to produce higher levels of IFN-γ after CD3 and CD28 costimulation than normal CD4+ T cells. Despite high-level IL-10R1 expression and constitutive STAT3 activation, IL-10-induced tyrosine phosphorylation of STAT3 is suppressed in RA CD4+ T cells, in contrast to normal CD4+ T cells, where STAT3 phosphorylation is dose-dependently inducible by IL-10. Serum IL-6 from RA patients induces STAT3 but not STAT1 phosphorylation in normal CD4+ T cells, and exogenous IL-6 induces the resistance to IL-10 inhibition of IFN-γ production. RA CD4+ T cells contain higher levels of SOCS1 but contain lower levels of SOCS3 transcripts in comparison with normal CD4+ T cells. These findings indicate that CD4+ T cells become resistant to the inhibitory effect of IL-10 before migration into the inflamed ST, and suggest that this resistance may be attributable to impaired IL-10-dependent STAT3 activation, in association with sustained STAT3 phosphorylation and SOCS1 induction."}
test3
{"project":"test3","denotations":[{"id":"T22528","span":{"begin":1394,"end":1403},"obj":"Positive_regulation"},{"id":"T22527","span":{"begin":1388,"end":1393},"obj":"Protein"},{"id":"T22526","span":{"begin":1368,"end":1383},"obj":"Phosphorylation"},{"id":"T22525","span":{"begin":1362,"end":1367},"obj":"Protein"},{"id":"T22524","span":{"begin":1352,"end":1361},"obj":"Positive_regulation"},{"id":"T22523","span":{"begin":1335,"end":1346},"obj":"Binding"},{"id":"T22522","span":{"begin":1320,"end":1330},"obj":"Positive_regulation"},{"id":"T22521","span":{"begin":1314,"end":1319},"obj":"Protein"},{"id":"T22520","span":{"begin":1304,"end":1313},"obj":"Regulation"},{"id":"T22519","span":{"begin":1298,"end":1303},"obj":"Protein"},{"id":"T22518","span":{"begin":1289,"end":1297},"obj":"Negative_regulation"},{"id":"T22517","span":{"begin":1188,"end":1193},"obj":"Protein"},{"id":"T22516","span":{"begin":1178,"end":1184},"obj":"Regulation"},{"id":"T22515","span":{"begin":1130,"end":1133},"obj":"Protein"},{"id":"T22514","span":{"begin":1087,"end":1090},"obj":"Protein"},{"id":"T22513","span":{"begin":1043,"end":1048},"obj":"Protein"},{"id":"T22512","span":{"begin":1009,"end":1014},"obj":"Protein"},{"id":"T22511","span":{"begin":971,"end":974},"obj":"Protein"},{"id":"T22510","span":{"begin":956,"end":966},"obj":"Gene_expression"},{"id":"T22509","span":{"begin":950,"end":955},"obj":"Protein"},{"id":"T22508","span":{"begin":936,"end":946},"obj":"Negative_regulation"},{"id":"T22507","span":{"begin":930,"end":935},"obj":"Protein"},{"id":"T22506","span":{"begin":904,"end":911},"obj":"Positive_regulation"},{"id":"T22505","span":{"begin":899,"end":903},"obj":"Protein"},{"id":"T22504","span":{"begin":871,"end":874},"obj":"Protein"},{"id":"T22503","span":{"begin":845,"end":860},"obj":"Phosphorylation"},{"id":"T22502","span":{"begin":839,"end":844},"obj":"Protein"},{"id":"T22501","span":{"begin":825,"end":830},"obj":"Protein"},{"id":"T22500","span":{"begin":817,"end":824},"obj":"Positive_regulation"},{"id":"T22499","span":{"begin":795,"end":799},"obj":"Protein"},{"id":"T22498","span":{"begin":782,"end":787},"obj":"Protein"},{"id":"T22497","span":{"begin":769,"end":778},"obj":"Positive_regulation"},{"id":"T22496","span":{"begin":733,"end":748},"obj":"Phosphorylation"},{"id":"T22495","span":{"begin":727,"end":732},"obj":"Protein"},{"id":"T22494","span":{"begin":707,"end":710},"obj":"Protein"},{"id":"T22493","span":{"begin":671,"end":674},"obj":"Protein"},{"id":"T22492","span":{"begin":654,"end":664},"obj":"Negative_regulation"},{"id":"T22491","span":{"begin":645,"end":650},"obj":"Protein"},{"id":"T22490","span":{"begin":626,"end":641},"obj":"Phosphorylation"},{"id":"T22489","span":{"begin":609,"end":616},"obj":"Positive_regulation"},{"id":"T22488","span":{"begin":603,"end":608},"obj":"Protein"},{"id":"T22487","span":{"begin":591,"end":601},"obj":"Positive_regulation"},{"id":"T22486","span":{"begin":585,"end":590},"obj":"Protein"},{"id":"T22485","span":{"begin":557,"end":567},"obj":"Gene_expression"},{"id":"T22484","span":{"begin":549,"end":556},"obj":"Protein"},{"id":"T22483","span":{"begin":538,"end":542},"obj":"Positive_regulation"},{"id":"T22482","span":{"begin":516,"end":519},"obj":"Protein"},{"id":"T22292","span":{"begin":1388,"end":1393},"obj":"Protein"},{"id":"T22291","span":{"begin":1362,"end":1367},"obj":"Protein"},{"id":"T22290","span":{"begin":1314,"end":1319},"obj":"Protein"},{"id":"T22289","span":{"begin":1298,"end":1303},"obj":"Protein"},{"id":"T22288","span":{"begin":1188,"end":1193},"obj":"Protein"},{"id":"T22287","span":{"begin":1130,"end":1133},"obj":"Protein"},{"id":"T22286","span":{"begin":1087,"end":1090},"obj":"Protein"},{"id":"T22285","span":{"begin":1043,"end":1048},"obj":"Protein"},{"id":"T22284","span":{"begin":1009,"end":1014},"obj":"Protein"},{"id":"T22283","span":{"begin":971,"end":974},"obj":"Protein"},{"id":"T22282","span":{"begin":950,"end":955},"obj":"Protein"},{"id":"T22281","span":{"begin":930,"end":935},"obj":"Protein"},{"id":"T22280","span":{"begin":899,"end":903},"obj":"Protein"},{"id":"T22279","span":{"begin":871,"end":874},"obj":"Protein"},{"id":"T22278","span":{"begin":839,"end":844},"obj":"Protein"},{"id":"T22277","span":{"begin":825,"end":830},"obj":"Protein"},{"id":"T22276","span":{"begin":795,"end":799},"obj":"Protein"},{"id":"T22275","span":{"begin":782,"end":787},"obj":"Protein"},{"id":"T22274","span":{"begin":727,"end":732},"obj":"Protein"},{"id":"T22273","span":{"begin":707,"end":710},"obj":"Protein"},{"id":"T22272","span":{"begin":671,"end":674},"obj":"Protein"},{"id":"T22271","span":{"begin":645,"end":650},"obj":"Protein"},{"id":"T22270","span":{"begin":603,"end":608},"obj":"Protein"},{"id":"T22269","span":{"begin":585,"end":590},"obj":"Protein"},{"id":"T22268","span":{"begin":549,"end":556},"obj":"Protein"},{"id":"T22267","span":{"begin":516,"end":519},"obj":"Protein"},{"id":"T22266","span":{"begin":485,"end":489},"obj":"Protein"},{"id":"T22265","span":{"begin":465,"end":470},"obj":"Protein"},{"id":"T22264","span":{"begin":421,"end":426},"obj":"Protein"},{"id":"T22263","span":{"begin":359,"end":362},"obj":"Protein"},{"id":"T22262","span":{"begin":194,"end":198},"obj":"Protein"},{"id":"T22261","span":{"begin":143,"end":148},"obj":"Protein"},{"id":"T22260","span":{"begin":0,"end":5},"obj":"Protein"},{"id":"T22481","span":{"begin":485,"end":489},"obj":"Protein"},{"id":"T22480","span":{"begin":465,"end":470},"obj":"Protein"},{"id":"T22479","span":{"begin":440,"end":447},"obj":"Gene_expression"},{"id":"T22478","span":{"begin":421,"end":426},"obj":"Protein"},{"id":"T22477","span":{"begin":359,"end":362},"obj":"Protein"},{"id":"T22476","span":{"begin":257,"end":264},"obj":"Binding"},{"id":"T22475","span":{"begin":194,"end":198},"obj":"Protein"},{"id":"T22474","span":{"begin":171,"end":186},"obj":"Phosphorylation"},{"id":"T22473","span":{"begin":149,"end":157},"obj":"Negative_regulation"},{"id":"T22472","span":{"begin":143,"end":148},"obj":"Protein"},{"id":"T22471","span":{"begin":0,"end":5},"obj":"Protein"}],"relations":[{"id":"R10993","pred":"causeOf","subj":"T22472","obj":"T22473"},{"id":"R10994","pred":"themeOf","subj":"T22474","obj":"T22473"},{"id":"R10995","pred":"themeOf","subj":"T22475","obj":"T22474"},{"id":"R10996","pred":"themeOf","subj":"T22480","obj":"T22479"},{"id":"R10997","pred":"themeOf","subj":"T22481","obj":"T22479"},{"id":"R10998","pred":"themeOf","subj":"T22484","obj":"T22485"},{"id":"R10999","pred":"themeOf","subj":"T22486","obj":"T22487"},{"id":"R11000","pred":"causeOf","subj":"T22488","obj":"T22489"},{"id":"R11001","pred":"themeOf","subj":"T22489","obj":"T22492"},{"id":"R11002","pred":"themeOf","subj":"T22490","obj":"T22489"},{"id":"R11003","pred":"themeOf","subj":"T22490","obj":"T22492"},{"id":"R11004","pred":"themeOf","subj":"T22491","obj":"T22490"},{"id":"R11005","pred":"themeOf","subj":"T22495","obj":"T22496"},{"id":"R11006","pred":"causeOf","subj":"T22498","obj":"T22497"},{"id":"R11007","pred":"causeOf","subj":"T22499","obj":"T22500"},{"id":"R11008","pred":"themeOf","subj":"T22501","obj":"T22503"},{"id":"R11009","pred":"themeOf","subj":"T22502","obj":"T22503"},{"id":"R11010","pred":"themeOf","subj":"T22503","obj":"T22500"},{"id":"R11011","pred":"causeOf","subj":"T22505","obj":"T22506"},{"id":"R11012","pred":"causeOf","subj":"T22507","obj":"T22508"},{"id":"R11013","pred":"themeOf","subj":"T22508","obj":"T22506"},{"id":"R11014","pred":"themeOf","subj":"T22509","obj":"T22510"},{"id":"R11015","pred":"themeOf","subj":"T22510","obj":"T22508"},{"id":"R11016","pred":"causeOf","subj":"T22519","obj":"T22520"},{"id":"R11017","pred":"themeOf","subj":"T22520","obj":"T22518"},{"id":"R11018","pred":"themeOf","subj":"T22521","obj":"T22522"},{"id":"R11019","pred":"themeOf","subj":"T22522","obj":"T22520"},{"id":"R11020","pred":"themeOf","subj":"T22525","obj":"T22526"},{"id":"R11021","pred":"themeOf","subj":"T22526","obj":"T22524"},{"id":"R11022","pred":"themeOf","subj":"T22527","obj":"T22528"},{"id":"R11023","pred":"themeOf","subj":"T22528","obj":"T22524"}],"text":"IL-10 plays a predominant role in limiting immune and inflammatory responses by regulating the function of both macrophages and Th1 cells [1]. IL-10 inhibits the tyrosine phosphorylation of the CD28 molecule and the subsequent phosphatidylinositol 3-kinase binding in T cells, and thereby directly acts on T cells [24]. In the present study, we found that PB CD4+ T cells from patients with active RA, in the presence of IL-10, are able to produce higher levels of IFN-γ after CD3 and CD28 costimulation than normal CD4+ T cells. Despite high-level IL-10R1 expression and constitutive STAT3 activation, IL-10-induced tyrosine phosphorylation of STAT3 is suppressed in RA CD4+ T cells, in contrast to normal CD4+ T cells, where STAT3 phosphorylation is dose-dependently inducible by IL-10. Serum IL-6 from RA patients induces STAT3 but not STAT1 phosphorylation in normal CD4+ T cells, and exogenous IL-6 induces the resistance to IL-10 inhibition of IFN-γ production. RA CD4+ T cells contain higher levels of SOCS1 but contain lower levels of SOCS3 transcripts in comparison with normal CD4+ T cells. These findings indicate that CD4+ T cells become resistant to the inhibitory effect of IL-10 before migration into the inflamed ST, and suggest that this resistance may be attributable to impaired IL-10-dependent STAT3 activation, in association with sustained STAT3 phosphorylation and SOCS1 induction."}
testone
{"project":"testone","denotations":[{"id":"T21760","span":{"begin":1388,"end":1393},"obj":"Protein"},{"id":"T21759","span":{"begin":1362,"end":1367},"obj":"Protein"},{"id":"T21758","span":{"begin":1314,"end":1319},"obj":"Protein"},{"id":"T21757","span":{"begin":1298,"end":1303},"obj":"Protein"},{"id":"T21756","span":{"begin":1188,"end":1193},"obj":"Protein"},{"id":"T21755","span":{"begin":1130,"end":1133},"obj":"Protein"},{"id":"T21754","span":{"begin":1087,"end":1090},"obj":"Protein"},{"id":"T21753","span":{"begin":1043,"end":1048},"obj":"Protein"},{"id":"T21752","span":{"begin":1009,"end":1014},"obj":"Protein"},{"id":"T21751","span":{"begin":971,"end":974},"obj":"Protein"},{"id":"T21750","span":{"begin":950,"end":955},"obj":"Protein"},{"id":"T21749","span":{"begin":930,"end":935},"obj":"Protein"},{"id":"T21748","span":{"begin":899,"end":903},"obj":"Protein"},{"id":"T21747","span":{"begin":871,"end":874},"obj":"Protein"},{"id":"T21746","span":{"begin":839,"end":844},"obj":"Protein"},{"id":"T21745","span":{"begin":825,"end":830},"obj":"Protein"},{"id":"T21744","span":{"begin":795,"end":799},"obj":"Protein"},{"id":"T21743","span":{"begin":782,"end":787},"obj":"Protein"},{"id":"T21742","span":{"begin":727,"end":732},"obj":"Protein"},{"id":"T21741","span":{"begin":707,"end":710},"obj":"Protein"},{"id":"T21740","span":{"begin":671,"end":674},"obj":"Protein"},{"id":"T21739","span":{"begin":645,"end":650},"obj":"Protein"},{"id":"T21738","span":{"begin":603,"end":608},"obj":"Protein"},{"id":"T21737","span":{"begin":585,"end":590},"obj":"Protein"},{"id":"T21736","span":{"begin":549,"end":556},"obj":"Protein"},{"id":"T21735","span":{"begin":516,"end":519},"obj":"Protein"},{"id":"T21734","span":{"begin":485,"end":489},"obj":"Protein"},{"id":"T21733","span":{"begin":465,"end":470},"obj":"Protein"},{"id":"T21732","span":{"begin":421,"end":426},"obj":"Protein"},{"id":"T21731","span":{"begin":359,"end":362},"obj":"Protein"},{"id":"T21730","span":{"begin":194,"end":198},"obj":"Protein"},{"id":"T21729","span":{"begin":143,"end":148},"obj":"Protein"},{"id":"T21728","span":{"begin":0,"end":5},"obj":"Protein"},{"id":"T21951","span":{"begin":1394,"end":1403},"obj":"Positive_regulation"},{"id":"T21950","span":{"begin":1368,"end":1383},"obj":"Phosphorylation"},{"id":"T21949","span":{"begin":1352,"end":1361},"obj":"Positive_regulation"},{"id":"T21948","span":{"begin":1335,"end":1346},"obj":"Binding"},{"id":"T21947","span":{"begin":1320,"end":1330},"obj":"Positive_regulation"},{"id":"T21946","span":{"begin":1304,"end":1313},"obj":"Positive_regulation"},{"id":"T21945","span":{"begin":1289,"end":1297},"obj":"Negative_regulation"},{"id":"T21944","span":{"begin":1273,"end":1285},"obj":"Positive_regulation"},{"id":"T21943","span":{"begin":956,"end":966},"obj":"Gene_expression"},{"id":"T21942","span":{"begin":936,"end":946},"obj":"Negative_regulation"},{"id":"T21941","span":{"begin":904,"end":911},"obj":"Positive_regulation"},{"id":"T21940","span":{"begin":845,"end":860},"obj":"Phosphorylation"},{"id":"T21939","span":{"begin":817,"end":824},"obj":"Positive_regulation"},{"id":"T21938","span":{"begin":769,"end":778},"obj":"Positive_regulation"},{"id":"T21937","span":{"begin":733,"end":748},"obj":"Phosphorylation"},{"id":"T21936","span":{"begin":654,"end":664},"obj":"Negative_regulation"},{"id":"T21935","span":{"begin":626,"end":641},"obj":"Phosphorylation"},{"id":"T21934","span":{"begin":609,"end":616},"obj":"Positive_regulation"},{"id":"T21933","span":{"begin":591,"end":601},"obj":"Positive_regulation"},{"id":"T21932","span":{"begin":557,"end":567},"obj":"Gene_expression"},{"id":"T21931","span":{"begin":448,"end":454},"obj":"Positive_regulation"},{"id":"T21930","span":{"begin":440,"end":447},"obj":"Gene_expression"},{"id":"T21929","span":{"begin":171,"end":186},"obj":"Phosphorylation"},{"id":"T21928","span":{"begin":149,"end":157},"obj":"Negative_regulation"}],"relations":[{"id":"R10843","pred":"causeOf","subj":"T21729","obj":"T21928"},{"id":"R10844","pred":"themeOf","subj":"T21733","obj":"T21930"},{"id":"R10845","pred":"themeOf","subj":"T21734","obj":"T21930"},{"id":"R10846","pred":"themeOf","subj":"T21736","obj":"T21932"},{"id":"R10847","pred":"themeOf","subj":"T21737","obj":"T21933"},{"id":"R10848","pred":"causeOf","subj":"T21738","obj":"T21934"},{"id":"R10849","pred":"themeOf","subj":"T21739","obj":"T21935"},{"id":"R10850","pred":"themeOf","subj":"T21742","obj":"T21937"},{"id":"R10851","pred":"causeOf","subj":"T21743","obj":"T21938"},{"id":"R10852","pred":"causeOf","subj":"T21744","obj":"T21939"},{"id":"R10853","pred":"themeOf","subj":"T21745","obj":"T21940"},{"id":"R10854","pred":"themeOf","subj":"T21746","obj":"T21940"},{"id":"R10855","pred":"causeOf","subj":"T21748","obj":"T21941"},{"id":"R10856","pred":"causeOf","subj":"T21749","obj":"T21942"},{"id":"R10857","pred":"themeOf","subj":"T21750","obj":"T21943"},{"id":"R10858","pred":"causeOf","subj":"T21757","obj":"T21946"},{"id":"R10859","pred":"themeOf","subj":"T21758","obj":"T21947"},{"id":"R10860","pred":"themeOf","subj":"T21759","obj":"T21950"},{"id":"R10861","pred":"themeOf","subj":"T21760","obj":"T21951"},{"id":"R10946","pred":"themeOf","subj":"T21929","obj":"T21928"},{"id":"R10947","pred":"themeOf","subj":"T21930","obj":"T21931"},{"id":"R10948","pred":"themeOf","subj":"T21934","obj":"T21936"},{"id":"R10949","pred":"themeOf","subj":"T21935","obj":"T21934"},{"id":"R10950","pred":"themeOf","subj":"T21935","obj":"T21936"},{"id":"R10951","pred":"themeOf","subj":"T21937","obj":"T21938"},{"id":"R10952","pred":"themeOf","subj":"T21940","obj":"T21939"},{"id":"R10953","pred":"themeOf","subj":"T21942","obj":"T21941"},{"id":"R10954","pred":"themeOf","subj":"T21943","obj":"T21942"},{"id":"R10955","pred":"themeOf","subj":"T21946","obj":"T21945"},{"id":"R10956","pred":"themeOf","subj":"T21947","obj":"T21946"},{"id":"R10957","pred":"themeOf","subj":"T21950","obj":"T21949"},{"id":"R10958","pred":"themeOf","subj":"T21951","obj":"T21949"}],"text":"IL-10 plays a predominant role in limiting immune and inflammatory responses by regulating the function of both macrophages and Th1 cells [1]. IL-10 inhibits the tyrosine phosphorylation of the CD28 molecule and the subsequent phosphatidylinositol 3-kinase binding in T cells, and thereby directly acts on T cells [24]. In the present study, we found that PB CD4+ T cells from patients with active RA, in the presence of IL-10, are able to produce higher levels of IFN-γ after CD3 and CD28 costimulation than normal CD4+ T cells. Despite high-level IL-10R1 expression and constitutive STAT3 activation, IL-10-induced tyrosine phosphorylation of STAT3 is suppressed in RA CD4+ T cells, in contrast to normal CD4+ T cells, where STAT3 phosphorylation is dose-dependently inducible by IL-10. Serum IL-6 from RA patients induces STAT3 but not STAT1 phosphorylation in normal CD4+ T cells, and exogenous IL-6 induces the resistance to IL-10 inhibition of IFN-γ production. RA CD4+ T cells contain higher levels of SOCS1 but contain lower levels of SOCS3 transcripts in comparison with normal CD4+ T cells. These findings indicate that CD4+ T cells become resistant to the inhibitory effect of IL-10 before migration into the inflamed ST, and suggest that this resistance may be attributable to impaired IL-10-dependent STAT3 activation, in association with sustained STAT3 phosphorylation and SOCS1 induction."}