PMC:2222968 / 159-1494 JSONTXT

{"project":"pmc-enju-pas","denotations":[{"id":"T121","span":{"begin":0,"end":13},"obj":"NN"},{"id":"T122","span":{"begin":14,"end":21},"obj":"NN"},{"id":"T123","span":{"begin":22,"end":25},"obj":"VB"},{"id":"T124","span":{"begin":26,"end":28},"obj":"IN"},{"id":"T125","span":{"begin":29,"end":36},"obj":"NN"},{"id":"T126","span":{"begin":37,"end":39},"obj":"TO"},{"id":"T127","span":{"begin":40,"end":46},"obj":"VB"},{"id":"T128","span":{"begin":47,"end":54},"obj":"NN"},{"id":"T129","span":{"begin":55,"end":65},"obj":"NN"},{"id":"T130","span":{"begin":66,"end":73},"obj":"IN"},{"id":"T131","span":{"begin":74,"end":77},"obj":"NN"},{"id":"T132","span":{"begin":77,"end":78},"obj":"-COMMA-"},{"id":"T133","span":{"begin":79,"end":82},"obj":"NN"},{"id":"T134","span":{"begin":82,"end":83},"obj":"-COMMA-"},{"id":"T135","span":{"begin":84,"end":86},"obj":"CC"},{"id":"T136","span":{"begin":87,"end":88},"obj":"NN"},{"id":"T137","span":{"begin":89,"end":99},"obj":"JJ"},{"id":"T138","span":{"begin":100,"end":101},"obj":"-LRB-"},{"id":"T139","span":{"begin":101,"end":105},"obj":"NN"},{"id":"T140","span":{"begin":105,"end":106},"obj":"-RRB-"},{"id":"T141","span":{"begin":107,"end":112},"obj":"NN"},{"id":"T142","span":{"begin":112,"end":113},"obj":"-COMMA-"},{"id":"T143","span":{"begin":114,"end":117},"obj":"CC"},{"id":"T144","span":{"begin":118,"end":123},"obj":"PRP-DOLLAR-"},{"id":"T145","span":{"begin":124,"end":142},"obj":"JJ"},{"id":"T146","span":{"begin":143,"end":153},"obj":"NN"},{"id":"T147","span":{"begin":154,"end":158},"obj":"VB"},{"id":"T148","span":{"begin":159,"end":164},"obj":"VB"},{"id":"T149","span":{"begin":165,"end":167},"obj":"TO"},{"id":"T150","span":{"begin":168,"end":170},"obj":"VB"},{"id":"T151","span":{"begin":171,"end":179},"obj":"JJ"},{"id":"T152","span":{"begin":180,"end":183},"obj":"IN"},{"id":"T153","span":{"begin":184,"end":196},"obj":"NN"},{"id":"T154","span":{"begin":197,"end":204},"obj":"IN"},{"id":"T155","span":{"begin":205,"end":208},"obj":"NN"},{"id":"T156","span":{"begin":209,"end":212},"obj":"CC"},{"id":"T157","span":{"begin":213,"end":216},"obj":"NN"},{"id":"T158","span":{"begin":217,"end":227},"obj":"NN"},{"id":"T159","span":{"begin":229,"end":234},"obj":"NN"},{"id":"T160","span":{"begin":235,"end":237},"obj":"VB"},{"id":"T161","span":{"begin":238,"end":240},"obj":"DT"},{"id":"T162","span":{"begin":241,"end":250},"obj":"JJ"},{"id":"T163","span":{"begin":251,"end":264},"obj":"NN"},{"id":"T164","span":{"begin":265,"end":271},"obj":"NN"},{"id":"T165","span":{"begin":272,"end":275},"obj":"IN"},{"id":"T166","span":{"begin":276,"end":283},"obj":"JJ"},{"id":"T167","span":{"begin":283,"end":284},"obj":"-COMMA-"},{"id":"T168","span":{"begin":285,"end":299},"obj":"JJ"},{"id":"T169","span":{"begin":300,"end":301},"obj":"-LRB-"},{"id":"T170","span":{"begin":301,"end":306},"obj":"NN"},{"id":"T171","span":{"begin":306,"end":307},"obj":"-RRB-"},{"id":"T172","span":{"begin":308,"end":311},"obj":"CC"},{"id":"T173","span":{"begin":312,"end":321},"obj":"JJ"},{"id":"T174","span":{"begin":322,"end":326},"obj":"NN"},{"id":"T175","span":{"begin":327,"end":328},"obj":"-LRB-"},{"id":"T176","span":{"begin":328,"end":333},"obj":"NN"},{"id":"T177","span":{"begin":333,"end":334},"obj":"-RRB-"},{"id":"T178","span":{"begin":335,"end":345},"obj":"NN"},{"id":"T179","span":{"begin":345,"end":346},"obj":"-COLON-"},{"id":"T180","span":{"begin":347,"end":354},"obj":"RB"},{"id":"T181","span":{"begin":354,"end":355},"obj":"-COMMA-"},{"id":"T182","span":{"begin":356,"end":359},"obj":"DT"},{"id":"T183","span":{"begin":360,"end":370},"obj":"NN"},{"id":"T184","span":{"begin":371,"end":381},"obj":"VB"},{"id":"T185","span":{"begin":382,"end":385},"obj":"PRP-DOLLAR-"},{"id":"T186","span":{"begin":386,"end":396},"obj":"NN"},{"id":"T187","span":{"begin":397,"end":400},"obj":"VB"},{"id":"T188","span":{"begin":401,"end":403},"obj":"RB"},{"id":"T189","span":{"begin":404,"end":407},"obj":"RB"},{"id":"T190","span":{"begin":408,"end":415},"obj":"JJ"},{"id":"T191","span":{"begin":417,"end":419},"obj":"PRP"},{"id":"T192","span":{"begin":420,"end":428},"obj":"VB"},{"id":"T193","span":{"begin":429,"end":430},"obj":"DT"},{"id":"T194","span":{"begin":431,"end":440},"obj":"NN"},{"id":"T195","span":{"begin":441,"end":452},"obj":"VB"},{"id":"T196","span":{"begin":453,"end":458},"obj":"NN"},{"id":"T197","span":{"begin":459,"end":471},"obj":"NN"},{"id":"T198","span":{"begin":471,"end":472},"obj":"-COMMA-"},{"id":"T199","span":{"begin":473,"end":478},"obj":"WDT"},{"id":"T200","span":{"begin":479,"end":481},"obj":"VB"},{"id":"T201","span":{"begin":482,"end":491},"obj":"VB"},{"id":"T202","span":{"begin":492,"end":494},"obj":"IN"},{"id":"T203","span":{"begin":495,"end":498},"obj":"DT"},{"id":"T204","span":{"begin":499,"end":502},"obj":"NN"},{"id":"T205","span":{"begin":503,"end":518},"obj":"NN"},{"id":"T206","span":{"begin":519,"end":526},"obj":"NN"},{"id":"T207","span":{"begin":528,"end":530},"obj":"PRP"},{"id":"T208","span":{"begin":531,"end":543},"obj":"VB"},{"id":"T209","span":{"begin":544,"end":548},"obj":"IN"},{"id":"T210","span":{"begin":549,"end":560},"obj":"NN"},{"id":"T211","span":{"begin":561,"end":562},"obj":"CD"},{"id":"T212","span":{"begin":563,"end":564},"obj":"-LRB-"},{"id":"T213","span":{"begin":564,"end":568},"obj":"NN"},{"id":"T214","span":{"begin":568,"end":569},"obj":"-RRB-"},{"id":"T215","span":{"begin":570,"end":577},"obj":"JJ"},{"id":"T216","span":{"begin":578,"end":580},"obj":"IN"},{"id":"T217","span":{"begin":581,"end":584},"obj":"DT"},{"id":"T218","span":{"begin":585,"end":589},"obj":"NN"},{"id":"T219","span":{"begin":590,"end":592},"obj":"IN"},{"id":"T220","span":{"begin":593,"end":594},"obj":"NN"},{"id":"T221","span":{"begin":595,"end":599},"obj":"NN"},{"id":"T222","span":{"begin":600,"end":607},"obj":"NN"},{"id":"T223","span":{"begin":608,"end":616},"obj":"VB"},{"id":"T224","span":{"begin":617,"end":622},"obj":"NN"},{"id":"T225","span":{"begin":624,"end":628},"obj":"DT"},{"id":"T226","span":{"begin":629,"end":639},"obj":"JJ"},{"id":"T227","span":{"begin":640,"end":649},"obj":"NN"},{"id":"T228","span":{"begin":650,"end":653},"obj":"VB"},{"id":"T229","span":{"begin":654,"end":658},"obj":"RB"},{"id":"T230","span":{"begin":659,"end":668},"obj":"VB"},{"id":"T231","span":{"begin":669,"end":671},"obj":"IN"},{"id":"T232","span":{"begin":672,"end":675},"obj":"NN"},{"id":"T233","span":{"begin":676,"end":681},"obj":"NN"},{"id":"T234","span":{"begin":682,"end":685},"obj":"CC"},{"id":"T235","span":{"begin":686,"end":688},"obj":"IN"},{"id":"T236","span":{"begin":689,"end":690},"obj":"NN"},{"id":"T237","span":{"begin":691,"end":696},"obj":"NN"},{"id":"T238","span":{"begin":697,"end":699},"obj":"IN"},{"id":"T239","span":{"begin":700,"end":710},"obj":"JJ"},{"id":"T240","span":{"begin":711,"end":715},"obj":"NN"},{"id":"T241","span":{"begin":716,"end":730},"obj":"VB"},{"id":"T242","span":{"begin":731,"end":737},"obj":"NN"},{"id":"T243","span":{"begin":738,"end":740},"obj":"IN"},{"id":"T244","span":{"begin":741,"end":742},"obj":"NN"},{"id":"T245","span":{"begin":743,"end":748},"obj":"NN"},{"id":"T246","span":{"begin":748,"end":749},"obj":"-COMMA-"},{"id":"T247","span":{"begin":750,"end":755},"obj":"WDT"},{"id":"T248","span":{"begin":756,"end":759},"obj":"VB"},{"id":"T249","span":{"begin":760,"end":765},"obj":"VB"},{"id":"T250","span":{"begin":766,"end":768},"obj":"TO"},{"id":"T251","span":{"begin":769,"end":771},"obj":"VB"},{"id":"T252","span":{"begin":772,"end":781},"obj":"JJ"},{"id":"T253","span":{"begin":782,"end":784},"obj":"IN"},{"id":"T254","span":{"begin":785,"end":797},"obj":"VB"},{"id":"T255","span":{"begin":798,"end":804},"obj":"NN"},{"id":"T256","span":{"begin":805,"end":811},"obj":"NN"},{"id":"T257","span":{"begin":812,"end":813},"obj":"-LRB-"},{"id":"T258","span":{"begin":813,"end":816},"obj":"NN"},{"id":"T259","span":{"begin":816,"end":817},"obj":"-RRB-"},{"id":"T260","span":{"begin":817,"end":828},"obj":"JJ"},{"id":"T261","span":{"begin":829,"end":834},"obj":"NN"},{"id":"T262","span":{"begin":835,"end":844},"obj":"NN"},{"id":"T263","span":{"begin":846,"end":850},"obj":"DT"},{"id":"T264","span":{"begin":851,"end":861},"obj":"NN"},{"id":"T265","span":{"begin":862,"end":864},"obj":"VB"},{"id":"T266","span":{"begin":865,"end":873},"obj":"VB"},{"id":"T267","span":{"begin":874,"end":876},"obj":"IN"},{"id":"T268","span":{"begin":877,"end":883},"obj":"JJ"},{"id":"T269","span":{"begin":884,"end":891},"obj":"NN"},{"id":"T270","span":{"begin":892,"end":894},"obj":"IN"},{"id":"T271","span":{"begin":895,"end":900},"obj":"NN"},{"id":"T272","span":{"begin":901,"end":903},"obj":"TO"},{"id":"T273","span":{"begin":904,"end":907},"obj":"DT"},{"id":"T274","span":{"begin":908,"end":913},"obj":"NN"},{"id":"T275","span":{"begin":914,"end":922},"obj":"NN"},{"id":"T276","span":{"begin":922,"end":923},"obj":"-COMMA-"},{"id":"T277","span":{"begin":924,"end":929},"obj":"WDT"},{"id":"T278","span":{"begin":930,"end":939},"obj":"VB"},{"id":"T279","span":{"begin":940,"end":943},"obj":"PRP-DOLLAR-"},{"id":"T280","span":{"begin":944,"end":959},"obj":"NN"},{"id":"T281","span":{"begin":960,"end":967},"obj":"NN"},{"id":"T282","span":{"begin":969,"end":978},"obj":"RB"},{"id":"T283","span":{"begin":978,"end":979},"obj":"-COMMA-"},{"id":"T284","span":{"begin":980,"end":984},"obj":"DT"},{"id":"T285","span":{"begin":985,"end":990},"obj":"NN"},{"id":"T286","span":{"begin":991,"end":999},"obj":"VB"},{"id":"T287","span":{"begin":1000,"end":1001},"obj":"DT"},{"id":"T288","span":{"begin":1002,"end":1005},"obj":"JJ"},{"id":"T289","span":{"begin":1006,"end":1019},"obj":"NN"},{"id":"T290","span":{"begin":1020,"end":1022},"obj":"IN"},{"id":"T291","span":{"begin":1023,"end":1032},"obj":"NN"},{"id":"T292","span":{"begin":1033,"end":1044},"obj":"NN"},{"id":"T293","span":{"begin":1044,"end":1045},"obj":"-COMMA-"},{"id":"T294","span":{"begin":1046,"end":1056},"obj":"VB"},{"id":"T295","span":{"begin":1057,"end":1059},"obj":"IN"},{"id":"T296","span":{"begin":1060,"end":1061},"obj":"DT"},{"id":"T297","span":{"begin":1062,"end":1066},"obj":"NN"},{"id":"T298","span":{"begin":1067,"end":1068},"obj":"CD"},{"id":"T299","span":{"begin":1069,"end":1075},"obj":"JJ"},{"id":"T300","span":{"begin":1076,"end":1084},"obj":"NN"},{"id":"T301","span":{"begin":1086,"end":1090},"obj":"NN"},{"id":"T302","span":{"begin":1091,"end":1100},"obj":"NN"},{"id":"T303","span":{"begin":1101,"end":1103},"obj":"IN"},{"id":"T304","span":{"begin":1104,"end":1108},"obj":"NN"},{"id":"T305","span":{"begin":1109,"end":1116},"obj":"VB"},{"id":"T306","span":{"begin":1117,"end":1122},"obj":"NN"},{"id":"T307","span":{"begin":1123,"end":1127},"obj":"NN"},{"id":"T308","span":{"begin":1128,"end":1137},"obj":"NN"},{"id":"T309","span":{"begin":1137,"end":1138},"obj":"-COMMA-"},{"id":"T310","span":{"begin":1139,"end":1151},"obj":"VB"},{"id":"T311","span":{"begin":1152,"end":1156},"obj":"IN"},{"id":"T312","span":{"begin":1157,"end":1168},"obj":"JJ"},{"id":"T313","span":{"begin":1169,"end":1179},"obj":"NN"},{"id":"T314","span":{"begin":1180,"end":1184},"obj":"WDT"},{"id":"T315","span":{"begin":1185,"end":1191},"obj":"VB"},{"id":"T316","span":{"begin":1192,"end":1196},"obj":"NN"},{"id":"T317","span":{"begin":1197,"end":1199},"obj":"CC"},{"id":"T318","span":{"begin":1200,"end":1205},"obj":"NN"},{"id":"T319","span":{"begin":1206,"end":1211},"obj":"MD"},{"id":"T320","span":{"begin":1212,"end":1219},"obj":"VB"},{"id":"T321","span":{"begin":1220,"end":1223},"obj":"JJ"},{"id":"T322","span":{"begin":1224,"end":1234},"obj":"JJ"},{"id":"T323","span":{"begin":1235,"end":1245},"obj":"NN"},{"id":"T324","span":{"begin":1246,"end":1258},"obj":"VB"},{"id":"T325","span":{"begin":1259,"end":1268},"obj":"NN"},{"id":"T326","span":{"begin":1269,"end":1278},"obj":"NN"},{"id":"T327","span":{"begin":1279,"end":1291},"obj":"RB"},{"id":"T328","span":{"begin":1292,"end":1294},"obj":"IN"},{"id":"T329","span":{"begin":1295,"end":1307},"obj":"JJ"},{"id":"T330","span":{"begin":1308,"end":1316},"obj":"NN"},{"id":"T331","span":{"begin":1316,"end":1317},"obj":"-COMMA-"},{"id":"T332","span":{"begin":1318,"end":1322},"obj":"JJ"},{"id":"T333","span":{"begin":1323,"end":1325},"obj":"IN"},{"id":"T334","span":{"begin":1326,"end":1333},"obj":"NN"}],"relations":[{"id":"R57","pred":"arg1Of","subj":"T122","obj":"T121"},{"id":"R58","pred":"arg1Of","subj":"T122","obj":"T123"},{"id":"R59","pred":"arg1Of","subj":"T122","obj":"T127"},{"id":"R60","pred":"arg1Of","subj":"T123","obj":"T124"},{"id":"R61","pred":"modOf","subj":"T123","obj":"T126"},{"id":"R62","pred":"arg1Of","subj":"T123","obj":"T143"},{"id":"R63","pred":"arg2Of","subj":"T125","obj":"T124"},{"id":"R64","pred":"arg1Of","subj":"T127","obj":"T126"},{"id":"R65","pred":"arg2Of","subj":"T129","obj":"T127"},{"id":"R66","pred":"arg1Of","subj":"T129","obj":"T128"},{"id":"R67","pred":"arg1Of","subj":"T129","obj":"T130"},{"id":"R68","pred":"arg1Of","subj":"T131","obj":"T132"},{"id":"R69","pred":"arg1Of","subj":"T132","obj":"T135"},{"id":"R70","pred":"arg2Of","subj":"T133","obj":"T132"},{"id":"R71","pred":"arg1Of","subj":"T135","obj":"T134"},{"id":"R72","pred":"arg2Of","subj":"T136","obj":"T135"},{"id":"R73","pred":"arg2Of","subj":"T139","obj":"T138"},{"id":"R74","pred":"arg3Of","subj":"T140","obj":"T138"},{"id":"R75","pred":"arg2Of","subj":"T141","obj":"T130"},{"id":"R76","pred":"arg1Of","subj":"T141","obj":"T131"},{"id":"R77","pred":"arg1Of","subj":"T141","obj":"T133"},{"id":"R78","pred":"arg1Of","subj":"T141","obj":"T136"},{"id":"R79","pred":"arg1Of","subj":"T141","obj":"T137"},{"id":"R80","pred":"arg1Of","subj":"T141","obj":"T138"},{"id":"R81","pred":"arg1Of","subj":"T143","obj":"T142"},{"id":"R82","pred":"arg1Of","subj":"T146","obj":"T144"},{"id":"R83","pred":"arg1Of","subj":"T146","obj":"T145"},{"id":"R84","pred":"arg1Of","subj":"T146","obj":"T147"},{"id":"R85","pred":"arg2Of","subj":"T146","obj":"T148"},{"id":"R86","pred":"arg1Of","subj":"T146","obj":"T150"},{"id":"R87","pred":"arg1Of","subj":"T146","obj":"T151"},{"id":"R88","pred":"arg2Of","subj":"T148","obj":"T143"},{"id":"R89","pred":"arg2Of","subj":"T148","obj":"T147"},{"id":"R90","pred":"arg3Of","subj":"T150","obj":"T148"},{"id":"R91","pred":"arg1Of","subj":"T150","obj":"T149"},{"id":"R92","pred":"arg2Of","subj":"T151","obj":"T150"},{"id":"R93","pred":"arg1Of","subj":"T151","obj":"T152"},{"id":"R94","pred":"arg2Of","subj":"T153","obj":"T152"},{"id":"R95","pred":"arg1Of","subj":"T153","obj":"T154"},{"id":"R96","pred":"arg1Of","subj":"T155","obj":"T156"},{"id":"R97","pred":"arg2Of","subj":"T157","obj":"T156"},{"id":"R98","pred":"arg2Of","subj":"T158","obj":"T154"},{"id":"R99","pred":"arg1Of","subj":"T158","obj":"T155"},{"id":"R100","pred":"arg1Of","subj":"T158","obj":"T157"},{"id":"R101","pred":"arg1Of","subj":"T159","obj":"T160"},{"id":"R102","pred":"arg1Of","subj":"T160","obj":"T179"},{"id":"R103","pred":"arg2Of","subj":"T164","obj":"T160"},{"id":"R104","pred":"arg1Of","subj":"T164","obj":"T161"},{"id":"R105","pred":"arg1Of","subj":"T164","obj":"T162"},{"id":"R106","pred":"arg1Of","subj":"T164","obj":"T163"},{"id":"R107","pred":"arg1Of","subj":"T164","obj":"T165"},{"id":"R108","pred":"arg1Of","subj":"T166","obj":"T167"},{"id":"R109","pred":"arg2Of","subj":"T168","obj":"T167"},{"id":"R110","pred":"arg1Of","subj":"T170","obj":"T166"},{"id":"R111","pred":"arg1Of","subj":"T170","obj":"T168"},{"id":"R112","pred":"arg2Of","subj":"T170","obj":"T169"},{"id":"R113","pred":"arg1Of","subj":"T170","obj":"T172"},{"id":"R114","pred":"arg3Of","subj":"T171","obj":"T169"},{"id":"R115","pred":"arg2Of","subj":"T172","obj":"T165"},{"id":"R116","pred":"arg2Of","subj":"T176","obj":"T175"},{"id":"R117","pred":"arg3Of","subj":"T177","obj":"T175"},{"id":"R118","pred":"arg2Of","subj":"T178","obj":"T172"},{"id":"R119","pred":"arg1Of","subj":"T178","obj":"T173"},{"id":"R120","pred":"arg1Of","subj":"T178","obj":"T174"},{"id":"R121","pred":"arg1Of","subj":"T178","obj":"T175"},{"id":"R122","pred":"arg1Of","subj":"T183","obj":"T182"},{"id":"R123","pred":"arg1Of","subj":"T183","obj":"T184"},{"id":"R124","pred":"arg1Of","subj":"T183","obj":"T187"},{"id":"R125","pred":"arg1Of","subj":"T183","obj":"T190"},{"id":"R126","pred":"arg2Of","subj":"T186","obj":"T184"},{"id":"R127","pred":"arg1Of","subj":"T186","obj":"T185"},{"id":"R128","pred":"arg2Of","subj":"T187","obj":"T179"},{"id":"R129","pred":"arg1Of","subj":"T187","obj":"T180"},{"id":"R130","pred":"arg1Of","subj":"T187","obj":"T181"},{"id":"R131","pred":"arg1Of","subj":"T187","obj":"T189"},{"id":"R132","pred":"arg1Of","subj":"T189","obj":"T188"},{"id":"R133","pred":"arg2Of","subj":"T190","obj":"T187"},{"id":"R134","pred":"arg1Of","subj":"T191","obj":"T192"},{"id":"R135","pred":"arg2Of","subj":"T194","obj":"T192"},{"id":"R136","pred":"arg1Of","subj":"T194","obj":"T193"},{"id":"R137","pred":"arg1Of","subj":"T194","obj":"T195"},{"id":"R138","pred":"arg2Of","subj":"T197","obj":"T195"},{"id":"R139","pred":"arg1Of","subj":"T197","obj":"T196"},{"id":"R140","pred":"arg1Of","subj":"T197","obj":"T198"},{"id":"R141","pred":"arg1Of","subj":"T197","obj":"T199"},{"id":"R142","pred":"arg1Of","subj":"T197","obj":"T200"},{"id":"R143","pred":"arg2Of","subj":"T197","obj":"T201"},{"id":"R144","pred":"arg2Of","subj":"T201","obj":"T200"},{"id":"R145","pred":"arg1Of","subj":"T206","obj":"T201"},{"id":"R146","pred":"arg2Of","subj":"T206","obj":"T202"},{"id":"R147","pred":"arg1Of","subj":"T206","obj":"T203"},{"id":"R148","pred":"arg1Of","subj":"T206","obj":"T204"},{"id":"R149","pred":"arg1Of","subj":"T206","obj":"T205"},{"id":"R150","pred":"arg1Of","subj":"T207","obj":"T208"},{"id":"R151","pred":"arg1Of","subj":"T210","obj":"T211"},{"id":"R152","pred":"arg1Of","subj":"T210","obj":"T212"},{"id":"R153","pred":"arg1Of","subj":"T210","obj":"T215"},{"id":"R154","pred":"arg1Of","subj":"T210","obj":"T223"},{"id":"R155","pred":"arg2Of","subj":"T213","obj":"T212"},{"id":"R156","pred":"arg3Of","subj":"T214","obj":"T212"},{"id":"R157","pred":"arg1Of","subj":"T215","obj":"T216"},{"id":"R158","pred":"arg2Of","subj":"T218","obj":"T216"},{"id":"R159","pred":"arg1Of","subj":"T218","obj":"T217"},{"id":"R160","pred":"arg1Of","subj":"T218","obj":"T219"},{"id":"R161","pred":"arg2Of","subj":"T222","obj":"T219"},{"id":"R162","pred":"arg1Of","subj":"T222","obj":"T220"},{"id":"R163","pred":"arg1Of","subj":"T222","obj":"T221"},{"id":"R164","pred":"arg2Of","subj":"T223","obj":"T208"},{"id":"R165","pred":"arg1Of","subj":"T223","obj":"T209"},{"id":"R166","pred":"arg2Of","subj":"T224","obj":"T223"},{"id":"R167","pred":"arg1Of","subj":"T227","obj":"T225"},{"id":"R168","pred":"arg1Of","subj":"T227","obj":"T226"},{"id":"R169","pred":"arg1Of","subj":"T227","obj":"T228"},{"id":"R170","pred":"arg2Of","subj":"T227","obj":"T230"},{"id":"R171","pred":"arg2Of","subj":"T230","obj":"T228"},{"id":"R172","pred":"arg1Of","subj":"T230","obj":"T229"},{"id":"R173","pred":"arg1Of","subj":"T230","obj":"T231"},{"id":"R174","pred":"arg1Of","subj":"T230","obj":"T235"},{"id":"R175","pred":"arg1Of","subj":"T231","obj":"T234"},{"id":"R176","pred":"arg2Of","subj":"T233","obj":"T231"},{"id":"R177","pred":"arg1Of","subj":"T233","obj":"T232"},{"id":"R178","pred":"arg2Of","subj":"T235","obj":"T234"},{"id":"R179","pred":"arg2Of","subj":"T237","obj":"T235"},{"id":"R180","pred":"arg1Of","subj":"T237","obj":"T236"},{"id":"R181","pred":"arg1Of","subj":"T237","obj":"T238"},{"id":"R182","pred":"arg2Of","subj":"T240","obj":"T238"},{"id":"R183","pred":"arg1Of","subj":"T240","obj":"T239"},{"id":"R184","pred":"arg1Of","subj":"T240","obj":"T241"},{"id":"R185","pred":"arg1Of","subj":"T240","obj":"T246"},{"id":"R186","pred":"arg1Of","subj":"T240","obj":"T247"},{"id":"R187","pred":"arg1Of","subj":"T240","obj":"T248"},{"id":"R188","pred":"arg2Of","subj":"T240","obj":"T249"},{"id":"R189","pred":"arg1Of","subj":"T240","obj":"T251"},{"id":"R190","pred":"arg1Of","subj":"T240","obj":"T252"},{"id":"R191","pred":"arg1Of","subj":"T241","obj":"T243"},{"id":"R192","pred":"arg2Of","subj":"T242","obj":"T241"},{"id":"R193","pred":"arg2Of","subj":"T245","obj":"T243"},{"id":"R194","pred":"arg1Of","subj":"T245","obj":"T244"},{"id":"R195","pred":"arg2Of","subj":"T249","obj":"T248"},{"id":"R196","pred":"arg3Of","subj":"T251","obj":"T249"},{"id":"R197","pred":"arg1Of","subj":"T251","obj":"T250"},{"id":"R198","pred":"arg2Of","subj":"T252","obj":"T251"},{"id":"R199","pred":"arg1Of","subj":"T252","obj":"T253"},{"id":"R200","pred":"arg2Of","subj":"T254","obj":"T253"},{"id":"R201","pred":"arg2Of","subj":"T258","obj":"T257"},{"id":"R202","pred":"arg3Of","subj":"T259","obj":"T257"},{"id":"R203","pred":"arg2Of","subj":"T262","obj":"T254"},{"id":"R204","pred":"arg1Of","subj":"T262","obj":"T255"},{"id":"R205","pred":"arg1Of","subj":"T262","obj":"T256"},{"id":"R206","pred":"arg1Of","subj":"T262","obj":"T257"},{"id":"R207","pred":"arg1Of","subj":"T262","obj":"T260"},{"id":"R208","pred":"arg1Of","subj":"T262","obj":"T261"},{"id":"R209","pred":"arg1Of","subj":"T264","obj":"T263"},{"id":"R210","pred":"arg1Of","subj":"T264","obj":"T265"},{"id":"R211","pred":"arg2Of","subj":"T264","obj":"T266"},{"id":"R212","pred":"arg2Of","subj":"T266","obj":"T265"},{"id":"R213","pred":"arg1Of","subj":"T269","obj":"T266"},{"id":"R214","pred":"arg2Of","subj":"T269","obj":"T267"},{"id":"R215","pred":"arg1Of","subj":"T269","obj":"T268"},{"id":"R216","pred":"arg1Of","subj":"T269","obj":"T270"},{"id":"R217","pred":"arg1Of","subj":"T269","obj":"T272"},{"id":"R218","pred":"arg1Of","subj":"T269","obj":"T276"},{"id":"R219","pred":"arg1Of","subj":"T269","obj":"T277"},{"id":"R220","pred":"arg1Of","subj":"T269","obj":"T278"},{"id":"R221","pred":"arg2Of","subj":"T271","obj":"T270"},{"id":"R222","pred":"arg2Of","subj":"T275","obj":"T272"},{"id":"R223","pred":"arg1Of","subj":"T275","obj":"T273"},{"id":"R224","pred":"arg1Of","subj":"T275","obj":"T274"},{"id":"R225","pred":"arg2Of","subj":"T281","obj":"T278"},{"id":"R226","pred":"arg1Of","subj":"T281","obj":"T279"},{"id":"R227","pred":"arg1Of","subj":"T281","obj":"T280"},{"id":"R228","pred":"arg1Of","subj":"T285","obj":"T284"},{"id":"R229","pred":"arg1Of","subj":"T285","obj":"T286"},{"id":"R230","pred":"arg1Of","subj":"T286","obj":"T282"},{"id":"R231","pred":"arg1Of","subj":"T286","obj":"T283"},{"id":"R232","pred":"arg2Of","subj":"T289","obj":"T286"},{"id":"R233","pred":"arg1Of","subj":"T289","obj":"T287"},{"id":"R234","pred":"arg1Of","subj":"T289","obj":"T288"},{"id":"R235","pred":"arg1Of","subj":"T289","obj":"T290"},{"id":"R236","pred":"arg1Of","subj":"T289","obj":"T293"},{"id":"R237","pred":"arg2Of","subj":"T289","obj":"T294"},{"id":"R238","pred":"arg2Of","subj":"T292","obj":"T290"},{"id":"R239","pred":"arg1Of","subj":"T292","obj":"T291"},{"id":"R240","pred":"arg1Of","subj":"T300","obj":"T294"},{"id":"R241","pred":"arg2Of","subj":"T300","obj":"T295"},{"id":"R242","pred":"arg1Of","subj":"T300","obj":"T296"},{"id":"R243","pred":"arg1Of","subj":"T300","obj":"T297"},{"id":"R244","pred":"arg1Of","subj":"T300","obj":"T298"},{"id":"R245","pred":"arg1Of","subj":"T300","obj":"T299"},{"id":"R246","pred":"arg1Of","subj":"T302","obj":"T301"},{"id":"R247","pred":"arg1Of","subj":"T302","obj":"T303"},{"id":"R248","pred":"arg1Of","subj":"T302","obj":"T305"},{"id":"R249","pred":"arg1Of","subj":"T302","obj":"T310"},{"id":"R250","pred":"arg2Of","subj":"T304","obj":"T303"},{"id":"R251","pred":"arg1Of","subj":"T305","obj":"T309"},{"id":"R252","pred":"modOf","subj":"T305","obj":"T310"},{"id":"R253","pred":"arg2Of","subj":"T308","obj":"T305"},{"id":"R254","pred":"arg1Of","subj":"T308","obj":"T306"},{"id":"R255","pred":"arg1Of","subj":"T308","obj":"T307"},{"id":"R256","pred":"arg1Of","subj":"T313","obj":"T312"},{"id":"R257","pred":"arg1Of","subj":"T313","obj":"T314"},{"id":"R258","pred":"arg1Of","subj":"T313","obj":"T315"},{"id":"R259","pred":"arg1Of","subj":"T313","obj":"T319"},{"id":"R260","pred":"arg1Of","subj":"T313","obj":"T320"},{"id":"R261","pred":"arg1Of","subj":"T316","obj":"T317"},{"id":"R262","pred":"arg2Of","subj":"T317","obj":"T315"},{"id":"R263","pred":"arg2Of","subj":"T318","obj":"T317"},{"id":"R264","pred":"arg2Of","subj":"T320","obj":"T310"},{"id":"R265","pred":"arg1Of","subj":"T320","obj":"T311"},{"id":"R266","pred":"arg2Of","subj":"T320","obj":"T319"},{"id":"R267","pred":"arg1Of","subj":"T320","obj":"T328"},{"id":"R268","pred":"arg2Of","subj":"T323","obj":"T320"},{"id":"R269","pred":"arg1Of","subj":"T323","obj":"T321"},{"id":"R270","pred":"arg1Of","subj":"T323","obj":"T322"},{"id":"R271","pred":"arg1Of","subj":"T323","obj":"T324"},{"id":"R272","pred":"arg2Of","subj":"T326","obj":"T324"},{"id":"R273","pred":"arg1Of","subj":"T326","obj":"T325"},{"id":"R274","pred":"arg1Of","subj":"T328","obj":"T327"},{"id":"R275","pred":"arg2Of","subj":"T330","obj":"T328"},{"id":"R276","pred":"arg1Of","subj":"T330","obj":"T329"},{"id":"R277","pred":"arg1Of","subj":"T330","obj":"T331"},{"id":"R278","pred":"arg1Of","subj":"T330","obj":"T333"},{"id":"R279","pred":"arg1Of","subj":"T333","obj":"T332"},{"id":"R280","pred":"arg2Of","subj":"T334","obj":"T333"}],"namespaces":[{"prefix":"_base","uri":"http://kmcs.nii.ac.jp/enju/"}],"text":"Transcription factors act in concert to induce lineage commitment towards Th1, Th2, or T regulatory (Treg) cells, and their counter-regulatory mechanisms were shown to be critical for polarization between Th1 and Th2 phenotypes. FOXP3 is an essential transcription factor for natural, thymus-derived (nTreg) and inducible Treg (iTreg) commitment; however, the mechanisms regulating its expression are as yet unknown. We describe a mechanism controlling iTreg polarization, which is overruled by the Th2 differentiation pathway. We demonstrated that interleukin 4 (IL-4) present at the time of T cell priming inhibits FOXP3. This inhibitory mechanism was also confirmed in Th2 cells and in T cells of transgenic mice overexpressing GATA-3 in T cells, which are shown to be deficient in transforming growth factor (TGF)-β–mediated FOXP3 induction. This inhibition is mediated by direct binding of GATA3 to the FOXP3 promoter, which represses its transactivation process. Therefore, this study provides a new understanding of tolerance development, controlled by a type 2 immune response. IL-4 treatment in mice reduces iTreg cell frequency, highlighting that therapeutic approaches that target IL-4 or GATA3 might provide new preventive strategies facilitating tolerance induction particularly in Th2-mediated diseases, such as allergy.\n"}

{"project":"bionlp-st-ge-2016-coref","denotations":[{"id":"T335","span":{"begin":382,"end":385},"obj":"Anaphor"},{"id":"T336","span":{"begin":229,"end":234},"obj":"Antecedent"},{"id":"T337","span":{"begin":846,"end":861},"obj":"Anaphor"},{"id":"T338","span":{"begin":772,"end":781},"obj":"Antecedent"}],"relations":[{"id":"R634","pred":"boundBy","subj":"T335","obj":"T336"},{"id":"R635","pred":"boundBy","subj":"T337","obj":"T338"}],"namespaces":[{"prefix":"_base","uri":"https://bionlp.dbcls.jp/ontology/ge.owl#"}],"text":"Transcription factors act in concert to induce lineage commitment towards Th1, Th2, or T regulatory (Treg) cells, and their counter-regulatory mechanisms were shown to be critical for polarization between Th1 and Th2 phenotypes. FOXP3 is an essential transcription factor for natural, thymus-derived (nTreg) and inducible Treg (iTreg) commitment; however, the mechanisms regulating its expression are as yet unknown. We describe a mechanism controlling iTreg polarization, which is overruled by the Th2 differentiation pathway. We demonstrated that interleukin 4 (IL-4) present at the time of T cell priming inhibits FOXP3. This inhibitory mechanism was also confirmed in Th2 cells and in T cells of transgenic mice overexpressing GATA-3 in T cells, which are shown to be deficient in transforming growth factor (TGF)-β–mediated FOXP3 induction. This inhibition is mediated by direct binding of GATA3 to the FOXP3 promoter, which represses its transactivation process. Therefore, this study provides a new understanding of tolerance development, controlled by a type 2 immune response. IL-4 treatment in mice reduces iTreg cell frequency, highlighting that therapeutic approaches that target IL-4 or GATA3 might provide new preventive strategies facilitating tolerance induction particularly in Th2-mediated diseases, such as allergy.\n"}

{"project":"bionlp-st-ge-2016-spacy-parsed","denotations":[{"id":"T376","span":{"begin":0,"end":13},"obj":"NNP"},{"id":"T377","span":{"begin":14,"end":21},"obj":"NNS"},{"id":"T378","span":{"begin":22,"end":25},"obj":"VBP"},{"id":"T379","span":{"begin":26,"end":28},"obj":"IN"},{"id":"T380","span":{"begin":29,"end":36},"obj":"NN"},{"id":"T381","span":{"begin":37,"end":39},"obj":"TO"},{"id":"T382","span":{"begin":40,"end":46},"obj":"VB"},{"id":"T383","span":{"begin":47,"end":54},"obj":"NN"},{"id":"T384","span":{"begin":55,"end":65},"obj":"NN"},{"id":"T385","span":{"begin":66,"end":73},"obj":"IN"},{"id":"T386","span":{"begin":74,"end":77},"obj":"NNP"},{"id":"T387","span":{"begin":77,"end":78},"obj":","},{"id":"T388","span":{"begin":79,"end":82},"obj":"NNP"},{"id":"T389","span":{"begin":82,"end":83},"obj":","},{"id":"T390","span":{"begin":84,"end":86},"obj":"CC"},{"id":"T391","span":{"begin":87,"end":88},"obj":"NNP"},{"id":"T392","span":{"begin":89,"end":99},"obj":"JJ"},{"id":"T393","span":{"begin":100,"end":101},"obj":"-LRB-"},{"id":"T394","span":{"begin":101,"end":105},"obj":"NNP"},{"id":"T395","span":{"begin":105,"end":106},"obj":"-RRB-"},{"id":"T396","span":{"begin":107,"end":112},"obj":"NNS"},{"id":"T397","span":{"begin":112,"end":113},"obj":","},{"id":"T398","span":{"begin":114,"end":117},"obj":"CC"},{"id":"T399","span":{"begin":118,"end":123},"obj":"PRP$"},{"id":"T400","span":{"begin":124,"end":142},"obj":"JJ"},{"id":"T401","span":{"begin":143,"end":153},"obj":"NNS"},{"id":"T402","span":{"begin":154,"end":158},"obj":"VBD"},{"id":"T403","span":{"begin":159,"end":164},"obj":"VBN"},{"id":"T404","span":{"begin":165,"end":167},"obj":"TO"},{"id":"T405","span":{"begin":168,"end":170},"obj":"VB"},{"id":"T406","span":{"begin":171,"end":179},"obj":"JJ"},{"id":"T407","span":{"begin":180,"end":183},"obj":"IN"},{"id":"T408","span":{"begin":184,"end":196},"obj":"NN"},{"id":"T409","span":{"begin":197,"end":204},"obj":"IN"},{"id":"T410","span":{"begin":205,"end":208},"obj":"CD"},{"id":"T411","span":{"begin":209,"end":212},"obj":"CC"},{"id":"T412","span":{"begin":213,"end":216},"obj":"CD"},{"id":"T413","span":{"begin":217,"end":227},"obj":"NNS"},{"id":"T414","span":{"begin":227,"end":228},"obj":"."},{"id":"T415","span":{"begin":229,"end":234},"obj":"CD"},{"id":"T416","span":{"begin":235,"end":237},"obj":"VBZ"},{"id":"T417","span":{"begin":238,"end":240},"obj":"DT"},{"id":"T418","span":{"begin":241,"end":250},"obj":"JJ"},{"id":"T419","span":{"begin":251,"end":264},"obj":"NN"},{"id":"T420","span":{"begin":265,"end":271},"obj":"NN"},{"id":"T421","span":{"begin":272,"end":275},"obj":"IN"},{"id":"T422","span":{"begin":276,"end":283},"obj":"JJ"},{"id":"T423","span":{"begin":283,"end":284},"obj":","},{"id":"T424","span":{"begin":285,"end":299},"obj":"JJ"},{"id":"T425","span":{"begin":300,"end":301},"obj":"-LRB-"},{"id":"T426","span":{"begin":301,"end":306},"obj":"NNP"},{"id":"T427","span":{"begin":306,"end":307},"obj":"-RRB-"},{"id":"T428","span":{"begin":308,"end":311},"obj":"CC"},{"id":"T429","span":{"begin":312,"end":321},"obj":"JJ"},{"id":"T430","span":{"begin":322,"end":326},"obj":"NNP"},{"id":"T431","span":{"begin":327,"end":328},"obj":"-LRB-"},{"id":"T432","span":{"begin":328,"end":333},"obj":"NNP"},{"id":"T433","span":{"begin":333,"end":334},"obj":"-RRB-"},{"id":"T434","span":{"begin":335,"end":345},"obj":"NN"},{"id":"T435","span":{"begin":345,"end":346},"obj":":"},{"id":"T436","span":{"begin":347,"end":354},"obj":"RB"},{"id":"T437","span":{"begin":354,"end":355},"obj":","},{"id":"T438","span":{"begin":356,"end":359},"obj":"DT"},{"id":"T439","span":{"begin":360,"end":370},"obj":"NNS"},{"id":"T440","span":{"begin":371,"end":381},"obj":"VBG"},{"id":"T441","span":{"begin":382,"end":385},"obj":"PRP$"},{"id":"T442","span":{"begin":386,"end":396},"obj":"NN"},{"id":"T443","span":{"begin":397,"end":400},"obj":"VBP"},{"id":"T444","span":{"begin":401,"end":403},"obj":"RB"},{"id":"T445","span":{"begin":404,"end":407},"obj":"RB"},{"id":"T446","span":{"begin":408,"end":415},"obj":"JJ"},{"id":"T447","span":{"begin":415,"end":416},"obj":"."},{"id":"T448","span":{"begin":417,"end":419},"obj":"PRP"},{"id":"T449","span":{"begin":420,"end":428},"obj":"VBP"},{"id":"T450","span":{"begin":429,"end":430},"obj":"DT"},{"id":"T451","span":{"begin":431,"end":440},"obj":"NN"},{"id":"T452","span":{"begin":441,"end":452},"obj":"VBG"},{"id":"T453","span":{"begin":453,"end":458},"obj":"NNP"},{"id":"T454","span":{"begin":459,"end":471},"obj":"NN"},{"id":"T455","span":{"begin":471,"end":472},"obj":","},{"id":"T456","span":{"begin":473,"end":478},"obj":"WDT"},{"id":"T457","span":{"begin":479,"end":481},"obj":"VBZ"},{"id":"T458","span":{"begin":482,"end":491},"obj":"VBN"},{"id":"T459","span":{"begin":492,"end":494},"obj":"IN"},{"id":"T460","span":{"begin":495,"end":498},"obj":"DT"},{"id":"T461","span":{"begin":499,"end":502},"obj":"JJ"},{"id":"T462","span":{"begin":503,"end":518},"obj":"NN"},{"id":"T463","span":{"begin":519,"end":526},"obj":"NN"},{"id":"T464","span":{"begin":526,"end":527},"obj":"."},{"id":"T465","span":{"begin":528,"end":530},"obj":"PRP"},{"id":"T466","span":{"begin":531,"end":543},"obj":"VBD"},{"id":"T467","span":{"begin":544,"end":548},"obj":"IN"},{"id":"T468","span":{"begin":549,"end":560},"obj":"NN"},{"id":"T469","span":{"begin":561,"end":562},"obj":"CD"},{"id":"T470","span":{"begin":563,"end":564},"obj":"-LRB-"},{"id":"T471","span":{"begin":564,"end":568},"obj":"NN"},{"id":"T472","span":{"begin":568,"end":569},"obj":"-RRB-"},{"id":"T473","span":{"begin":570,"end":577},"obj":"NN"},{"id":"T474","span":{"begin":578,"end":580},"obj":"IN"},{"id":"T475","span":{"begin":581,"end":584},"obj":"DT"},{"id":"T476","span":{"begin":585,"end":589},"obj":"NN"},{"id":"T477","span":{"begin":590,"end":592},"obj":"IN"},{"id":"T478","span":{"begin":593,"end":594},"obj":"NNP"},{"id":"T479","span":{"begin":595,"end":599},"obj":"NN"},{"id":"T480","span":{"begin":600,"end":607},"obj":"VBG"},{"id":"T481","span":{"begin":608,"end":616},"obj":"NNS"},{"id":"T482","span":{"begin":617,"end":622},"obj":"NNP"},{"id":"T483","span":{"begin":622,"end":623},"obj":"."},{"id":"T484","span":{"begin":624,"end":628},"obj":"DT"},{"id":"T485","span":{"begin":629,"end":639},"obj":"JJ"},{"id":"T486","span":{"begin":640,"end":649},"obj":"NN"},{"id":"T487","span":{"begin":650,"end":653},"obj":"VBD"},{"id":"T488","span":{"begin":654,"end":658},"obj":"RB"},{"id":"T489","span":{"begin":659,"end":668},"obj":"VBN"},{"id":"T490","span":{"begin":669,"end":671},"obj":"IN"},{"id":"T491","span":{"begin":672,"end":675},"obj":"JJ"},{"id":"T492","span":{"begin":676,"end":681},"obj":"NNS"},{"id":"T493","span":{"begin":682,"end":685},"obj":"CC"},{"id":"T494","span":{"begin":686,"end":688},"obj":"IN"},{"id":"T495","span":{"begin":689,"end":690},"obj":"NNP"},{"id":"T496","span":{"begin":691,"end":696},"obj":"NNS"},{"id":"T497","span":{"begin":697,"end":699},"obj":"IN"},{"id":"T498","span":{"begin":700,"end":710},"obj":"JJ"},{"id":"T499","span":{"begin":711,"end":715},"obj":"NNS"},{"id":"T500","span":{"begin":716,"end":730},"obj":"VBG"},{"id":"T501","span":{"begin":731,"end":737},"obj":"NN"},{"id":"T502","span":{"begin":738,"end":740},"obj":"IN"},{"id":"T503","span":{"begin":741,"end":742},"obj":"NNP"},{"id":"T504","span":{"begin":743,"end":748},"obj":"NNS"},{"id":"T505","span":{"begin":748,"end":749},"obj":","},{"id":"T506","span":{"begin":750,"end":755},"obj":"WDT"},{"id":"T507","span":{"begin":756,"end":759},"obj":"VBP"},{"id":"T508","span":{"begin":760,"end":765},"obj":"VBN"},{"id":"T509","span":{"begin":766,"end":768},"obj":"TO"},{"id":"T510","span":{"begin":769,"end":771},"obj":"VB"},{"id":"T511","span":{"begin":772,"end":781},"obj":"JJ"},{"id":"T512","span":{"begin":782,"end":784},"obj":"IN"},{"id":"T513","span":{"begin":785,"end":797},"obj":"VBG"},{"id":"T514","span":{"begin":798,"end":804},"obj":"NN"},{"id":"T515","span":{"begin":805,"end":811},"obj":"NN"},{"id":"T516","span":{"begin":812,"end":813},"obj":"-LRB-"},{"id":"T517","span":{"begin":813,"end":816},"obj":"NNP"},{"id":"T518","span":{"begin":816,"end":817},"obj":"-RRB-"},{"id":"T519","span":{"begin":817,"end":818},"obj":":"},{"id":"T520","span":{"begin":818,"end":819},"obj":"NN"},{"id":"T521","span":{"begin":820,"end":828},"obj":"VBD"},{"id":"T522","span":{"begin":829,"end":834},"obj":"CD"},{"id":"T523","span":{"begin":835,"end":844},"obj":"NN"},{"id":"T524","span":{"begin":844,"end":845},"obj":"."},{"id":"T525","span":{"begin":846,"end":850},"obj":"DT"},{"id":"T526","span":{"begin":851,"end":861},"obj":"NN"},{"id":"T527","span":{"begin":862,"end":864},"obj":"VBZ"},{"id":"T528","span":{"begin":865,"end":873},"obj":"VBN"},{"id":"T529","span":{"begin":874,"end":876},"obj":"IN"},{"id":"T530","span":{"begin":877,"end":883},"obj":"JJ"},{"id":"T531","span":{"begin":884,"end":891},"obj":"JJ"},{"id":"T532","span":{"begin":892,"end":894},"obj":"IN"},{"id":"T533","span":{"begin":895,"end":900},"obj":"CD"},{"id":"T534","span":{"begin":901,"end":903},"obj":"TO"},{"id":"T535","span":{"begin":904,"end":907},"obj":"DT"},{"id":"T536","span":{"begin":908,"end":913},"obj":"CD"},{"id":"T537","span":{"begin":914,"end":922},"obj":"NN"},{"id":"T538","span":{"begin":922,"end":923},"obj":","},{"id":"T539","span":{"begin":924,"end":929},"obj":"WDT"},{"id":"T540","span":{"begin":930,"end":939},"obj":"VBZ"},{"id":"T541","span":{"begin":940,"end":943},"obj":"PRP$"},{"id":"T542","span":{"begin":944,"end":959},"obj":"NN"},{"id":"T543","span":{"begin":960,"end":967},"obj":"NN"},{"id":"T544","span":{"begin":967,"end":968},"obj":"."},{"id":"T545","span":{"begin":969,"end":978},"obj":"RB"},{"id":"T546","span":{"begin":978,"end":979},"obj":","},{"id":"T547","span":{"begin":980,"end":984},"obj":"DT"},{"id":"T548","span":{"begin":985,"end":990},"obj":"NN"},{"id":"T549","span":{"begin":991,"end":999},"obj":"VBZ"},{"id":"T550","span":{"begin":1000,"end":1001},"obj":"DT"},{"id":"T551","span":{"begin":1002,"end":1005},"obj":"JJ"},{"id":"T552","span":{"begin":1006,"end":1019},"obj":"NN"},{"id":"T553","span":{"begin":1020,"end":1022},"obj":"IN"},{"id":"T554","span":{"begin":1023,"end":1032},"obj":"NN"},{"id":"T555","span":{"begin":1033,"end":1044},"obj":"NN"},{"id":"T556","span":{"begin":1044,"end":1045},"obj":","},{"id":"T557","span":{"begin":1046,"end":1056},"obj":"VBN"},{"id":"T558","span":{"begin":1057,"end":1059},"obj":"IN"},{"id":"T559","span":{"begin":1060,"end":1061},"obj":"DT"},{"id":"T560","span":{"begin":1062,"end":1066},"obj":"NN"},{"id":"T561","span":{"begin":1067,"end":1068},"obj":"CD"},{"id":"T562","span":{"begin":1069,"end":1075},"obj":"JJ"},{"id":"T563","span":{"begin":1076,"end":1084},"obj":"NN"},{"id":"T564","span":{"begin":1084,"end":1085},"obj":"."},{"id":"T565","span":{"begin":1086,"end":1090},"obj":"NN"},{"id":"T566","span":{"begin":1091,"end":1100},"obj":"NN"},{"id":"T567","span":{"begin":1101,"end":1103},"obj":"IN"},{"id":"T568","span":{"begin":1104,"end":1108},"obj":"NNS"},{"id":"T569","span":{"begin":1109,"end":1116},"obj":"VBZ"},{"id":"T570","span":{"begin":1117,"end":1122},"obj":"NNP"},{"id":"T571","span":{"begin":1123,"end":1127},"obj":"NN"},{"id":"T572","span":{"begin":1128,"end":1137},"obj":"NN"},{"id":"T573","span":{"begin":1137,"end":1138},"obj":","},{"id":"T574","span":{"begin":1139,"end":1151},"obj":"VBG"},{"id":"T575","span":{"begin":1152,"end":1156},"obj":"IN"},{"id":"T576","span":{"begin":1157,"end":1168},"obj":"JJ"},{"id":"T577","span":{"begin":1169,"end":1179},"obj":"NNS"},{"id":"T578","span":{"begin":1180,"end":1184},"obj":"WDT"},{"id":"T579","span":{"begin":1185,"end":1191},"obj":"VBP"},{"id":"T580","span":{"begin":1192,"end":1196},"obj":"NN"},{"id":"T581","span":{"begin":1197,"end":1199},"obj":"CC"},{"id":"T582","span":{"begin":1200,"end":1205},"obj":"NN"},{"id":"T583","span":{"begin":1206,"end":1211},"obj":"MD"},{"id":"T584","span":{"begin":1212,"end":1219},"obj":"VB"},{"id":"T585","span":{"begin":1220,"end":1223},"obj":"JJ"},{"id":"T586","span":{"begin":1224,"end":1234},"obj":"JJ"},{"id":"T587","span":{"begin":1235,"end":1245},"obj":"NNS"},{"id":"T588","span":{"begin":1246,"end":1258},"obj":"VBG"},{"id":"T589","span":{"begin":1259,"end":1268},"obj":"NN"},{"id":"T590","span":{"begin":1269,"end":1278},"obj":"NN"},{"id":"T591","span":{"begin":1279,"end":1291},"obj":"RB"},{"id":"T592","span":{"begin":1292,"end":1294},"obj":"IN"},{"id":"T593","span":{"begin":1295,"end":1307},"obj":"JJ"},{"id":"T594","span":{"begin":1308,"end":1316},"obj":"NNS"},{"id":"T595","span":{"begin":1316,"end":1317},"obj":","},{"id":"T596","span":{"begin":1318,"end":1322},"obj":"JJ"},{"id":"T597","span":{"begin":1323,"end":1325},"obj":"IN"},{"id":"T598","span":{"begin":1326,"end":1333},"obj":"NN"},{"id":"T599","span":{"begin":1333,"end":1334},"obj":"."}],"relations":[{"id":"R296","pred":"compound","subj":"T376","obj":"T377"},{"id":"R299","pred":"prep","subj":"T379","obj":"T378"},{"id":"R300","pred":"pobj","subj":"T380","obj":"T379"},{"id":"R301","pred":"aux","subj":"T381","obj":"T382"},{"id":"R302","pred":"advcl","subj":"T382","obj":"T378"},{"id":"R303","pred":"compound","subj":"T383","obj":"T384"},{"id":"R304","pred":"dobj","subj":"T384","obj":"T382"},{"id":"R305","pred":"prep","subj":"T385","obj":"T384"},{"id":"R306","pred":"pobj","subj":"T386","obj":"T385"},{"id":"R307","pred":"punct","subj":"T387","obj":"T386"},{"id":"R308","pred":"conj","subj":"T388","obj":"T386"},{"id":"R309","pred":"punct","subj":"T389","obj":"T388"},{"id":"R310","pred":"cc","subj":"T390","obj":"T388"},{"id":"R311","pred":"conj","subj":"T391","obj":"T388"},{"id":"R312","pred":"amod","subj":"T392","obj":"T396"},{"id":"R313","pred":"punct","subj":"T393","obj":"T394"},{"id":"R314","pred":"appos","subj":"T394","obj":"T392"},{"id":"R315","pred":"punct","subj":"T395","obj":"T394"},{"id":"R316","pred":"pobj","subj":"T396","obj":"T385"},{"id":"R317","pred":"punct","subj":"T397","obj":"T378"},{"id":"R318","pred":"cc","subj":"T398","obj":"T378"},{"id":"R319","pred":"poss","subj":"T399","obj":"T401"},{"id":"R320","pred":"amod","subj":"T400","obj":"T401"},{"id":"R321","pred":"nsubjpass","subj":"T401","obj":"T403"},{"id":"R378","pred":"relcl","subj":"T458","obj":"T454"},{"id":"R379","pred":"agent","subj":"T459","obj":"T458"},{"id":"R380","pred":"det","subj":"T460","obj":"T463"},{"id":"R381","pred":"amod","subj":"T461","obj":"T463"},{"id":"R382","pred":"compound","subj":"T462","obj":"T463"},{"id":"R383","pred":"pobj","subj":"T463","obj":"T459"},{"id":"R384","pred":"punct","subj":"T464","obj":"T449"},{"id":"R385","pred":"nsubj","subj":"T465","obj":"T466"},{"id":"R386","pred":"ROOT","subj":"T466","obj":"T466"},{"id":"R387","pred":"mark","subj":"T467","obj":"T481"},{"id":"R388","pred":"nsubj","subj":"T468","obj":"T481"},{"id":"R389","pred":"nummod","subj":"T469","obj":"T468"},{"id":"R390","pred":"punct","subj":"T470","obj":"T471"},{"id":"R391","pred":"appos","subj":"T471","obj":"T468"},{"id":"R392","pred":"punct","subj":"T472","obj":"T471"},{"id":"R393","pred":"amod","subj":"T473","obj":"T468"},{"id":"R394","pred":"prep","subj":"T474","obj":"T468"},{"id":"R395","pred":"det","subj":"T475","obj":"T476"},{"id":"R396","pred":"pobj","subj":"T476","obj":"T474"},{"id":"R397","pred":"prep","subj":"T477","obj":"T476"},{"id":"R398","pred":"compound","subj":"T478","obj":"T479"},{"id":"R399","pred":"compound","subj":"T479","obj":"T480"},{"id":"R400","pred":"nsubj","subj":"T480","obj":"T481"},{"id":"R401","pred":"ccomp","subj":"T481","obj":"T466"},{"id":"R402","pred":"dobj","subj":"T482","obj":"T481"},{"id":"R403","pred":"punct","subj":"T483","obj":"T466"},{"id":"R404","pred":"det","subj":"T484","obj":"T486"},{"id":"R405","pred":"amod","subj":"T485","obj":"T486"},{"id":"R406","pred":"nsubjpass","subj":"T486","obj":"T489"},{"id":"R407","pred":"auxpass","subj":"T487","obj":"T489"},{"id":"R408","pred":"advmod","subj":"T488","obj":"T489"},{"id":"R409","pred":"ROOT","subj":"T489","obj":"T489"},{"id":"R410","pred":"prep","subj":"T490","obj":"T489"},{"id":"R411","pred":"amod","subj":"T491","obj":"T492"},{"id":"R412","pred":"pobj","subj":"T492","obj":"T490"},{"id":"R413","pred":"cc","subj":"T493","obj":"T490"},{"id":"R414","pred":"conj","subj":"T494","obj":"T490"},{"id":"R415","pred":"compound","subj":"T495","obj":"T496"},{"id":"R416","pred":"pobj","subj":"T496","obj":"T494"},{"id":"R417","pred":"prep","subj":"T497","obj":"T496"},{"id":"R418","pred":"amod","subj":"T498","obj":"T499"},{"id":"R419","pred":"pobj","subj":"T499","obj":"T497"},{"id":"R420","pred":"advcl","subj":"T500","obj":"T489"},{"id":"R421","pred":"dobj","subj":"T501","obj":"T500"},{"id":"R422","pred":"prep","subj":"T502","obj":"T500"},{"id":"R423","pred":"compound","subj":"T503","obj":"T504"},{"id":"R424","pred":"pobj","subj":"T504","obj":"T502"},{"id":"R425","pred":"punct","subj":"T505","obj":"T489"},{"id":"R426","pred":"nsubjpass","subj":"T506","obj":"T508"},{"id":"R427","pred":"auxpass","subj":"T507","obj":"T508"},{"id":"R428","pred":"advcl","subj":"T508","obj":"T489"},{"id":"R429","pred":"aux","subj":"T509","obj":"T510"},{"id":"R430","pred":"xcomp","subj":"T510","obj":"T508"},{"id":"R431","pred":"acomp","subj":"T511","obj":"T510"},{"id":"R432","pred":"prep","subj":"T512","obj":"T511"},{"id":"R433","pred":"pcomp","subj":"T513","obj":"T512"},{"id":"R434","pred":"compound","subj":"T514","obj":"T515"},{"id":"R435","pred":"dobj","subj":"T515","obj":"T513"},{"id":"R436","pred":"punct","subj":"T516","obj":"T517"},{"id":"R437","pred":"appos","subj":"T517","obj":"T515"},{"id":"R438","pred":"punct","subj":"T518","obj":"T517"},{"id":"R439","pred":"punct","subj":"T519","obj":"T515"},{"id":"R440","pred":"appos","subj":"T520","obj":"T515"},{"id":"R441","pred":"conj","subj":"T521","obj":"T489"},{"id":"R442","pred":"nummod","subj":"T522","obj":"T523"},{"id":"R443","pred":"dobj","subj":"T523","obj":"T521"},{"id":"R444","pred":"punct","subj":"T524","obj":"T489"},{"id":"R445","pred":"det","subj":"T525","obj":"T526"},{"id":"R446","pred":"nsubjpass","subj":"T526","obj":"T528"},{"id":"R447","pred":"auxpass","subj":"T527","obj":"T528"},{"id":"R448","pred":"ROOT","subj":"T528","obj":"T528"},{"id":"R449","pred":"agent","subj":"T529","obj":"T528"},{"id":"R450","pred":"amod","subj":"T530","obj":"T531"},{"id":"R451","pred":"pobj","subj":"T531","obj":"T529"},{"id":"R452","pred":"prep","subj":"T532","obj":"T531"},{"id":"R453","pred":"pobj","subj":"T533","obj":"T532"},{"id":"R454","pred":"prep","subj":"T534","obj":"T528"},{"id":"R455","pred":"det","subj":"T535","obj":"T537"},{"id":"R456","pred":"nummod","subj":"T536","obj":"T537"},{"id":"R457","pred":"pobj","subj":"T537","obj":"T534"},{"id":"R458","pred":"punct","subj":"T538","obj":"T537"},{"id":"R459","pred":"nsubj","subj":"T539","obj":"T540"},{"id":"R460","pred":"relcl","subj":"T540","obj":"T537"},{"id":"R461","pred":"poss","subj":"T541","obj":"T543"},{"id":"R462","pred":"compound","subj":"T542","obj":"T543"},{"id":"R463","pred":"dobj","subj":"T543","obj":"T540"},{"id":"R464","pred":"punct","subj":"T544","obj":"T528"},{"id":"R465","pred":"advmod","subj":"T545","obj":"T549"},{"id":"R466","pred":"punct","subj":"T546","obj":"T549"},{"id":"R467","pred":"det","subj":"T547","obj":"T548"},{"id":"R468","pred":"nsubj","subj":"T548","obj":"T549"},{"id":"R469","pred":"ROOT","subj":"T549","obj":"T549"},{"id":"R470","pred":"det","subj":"T550","obj":"T552"},{"id":"R471","pred":"amod","subj":"T551","obj":"T552"},{"id":"R472","pred":"dobj","subj":"T552","obj":"T549"},{"id":"R473","pred":"prep","subj":"T553","obj":"T552"},{"id":"R474","pred":"compound","subj":"T554","obj":"T555"},{"id":"R475","pred":"pobj","subj":"T555","obj":"T553"},{"id":"R476","pred":"punct","subj":"T556","obj":"T552"},{"id":"R477","pred":"acl","subj":"T557","obj":"T552"},{"id":"R478","pred":"agent","subj":"T558","obj":"T557"},{"id":"R479","pred":"det","subj":"T559","obj":"T563"},{"id":"R480","pred":"nmod","subj":"T560","obj":"T563"},{"id":"R481","pred":"nummod","subj":"T561","obj":"T560"},{"id":"R482","pred":"amod","subj":"T562","obj":"T563"},{"id":"R483","pred":"pobj","subj":"T563","obj":"T558"},{"id":"R484","pred":"punct","subj":"T564","obj":"T549"},{"id":"R485","pred":"compound","subj":"T565","obj":"T566"},{"id":"R486","pred":"nsubj","subj":"T566","obj":"T569"},{"id":"R487","pred":"prep","subj":"T567","obj":"T566"},{"id":"R488","pred":"pobj","subj":"T568","obj":"T567"},{"id":"R489","pred":"ROOT","subj":"T569","obj":"T569"},{"id":"R490","pred":"compound","subj":"T570","obj":"T572"},{"id":"R491","pred":"compound","subj":"T571","obj":"T572"},{"id":"R492","pred":"dobj","subj":"T572","obj":"T569"},{"id":"R493","pred":"punct","subj":"T573","obj":"T569"},{"id":"R494","pred":"advcl","subj":"T574","obj":"T569"},{"id":"R495","pred":"mark","subj":"T575","obj":"T584"},{"id":"R496","pred":"amod","subj":"T576","obj":"T577"},{"id":"R497","pred":"nsubj","subj":"T577","obj":"T584"},{"id":"R498","pred":"nsubj","subj":"T578","obj":"T579"},{"id":"R499","pred":"relcl","subj":"T579","obj":"T577"},{"id":"R500","pred":"dobj","subj":"T580","obj":"T579"},{"id":"R501","pred":"cc","subj":"T581","obj":"T580"},{"id":"R502","pred":"conj","subj":"T582","obj":"T580"},{"id":"R503","pred":"aux","subj":"T583","obj":"T584"},{"id":"R504","pred":"ccomp","subj":"T584","obj":"T574"},{"id":"R505","pred":"amod","subj":"T585","obj":"T587"},{"id":"R506","pred":"amod","subj":"T586","obj":"T587"},{"id":"R507","pred":"dobj","subj":"T587","obj":"T584"},{"id":"R508","pred":"advcl","subj":"T588","obj":"T584"},{"id":"R509","pred":"compound","subj":"T589","obj":"T590"},{"id":"R510","pred":"dobj","subj":"T590","obj":"T588"},{"id":"R511","pred":"advmod","subj":"T591","obj":"T592"},{"id":"R512","pred":"prep","subj":"T592","obj":"T590"},{"id":"R513","pred":"amod","subj":"T593","obj":"T594"},{"id":"R514","pred":"pobj","subj":"T594","obj":"T592"},{"id":"R515","pred":"punct","subj":"T595","obj":"T594"},{"id":"R516","pred":"amod","subj":"T596","obj":"T597"},{"id":"R517","pred":"prep","subj":"T597","obj":"T594"},{"id":"R518","pred":"pobj","subj":"T598","obj":"T597"},{"id":"R519","pred":"punct","subj":"T599","obj":"T569"},{"id":"R322","pred":"auxpass","subj":"T402","obj":"T403"},{"id":"R323","pred":"conj","subj":"T403","obj":"T378"},{"id":"R324","pred":"aux","subj":"T404","obj":"T405"},{"id":"R325","pred":"xcomp","subj":"T405","obj":"T403"},{"id":"R326","pred":"acomp","subj":"T406","obj":"T405"},{"id":"R327","pred":"prep","subj":"T407","obj":"T406"},{"id":"R328","pred":"pobj","subj":"T408","obj":"T407"},{"id":"R329","pred":"prep","subj":"T409","obj":"T408"},{"id":"R330","pred":"nummod","subj":"T410","obj":"T413"},{"id":"R331","pred":"cc","subj":"T411","obj":"T410"},{"id":"R332","pred":"conj","subj":"T412","obj":"T410"},{"id":"R333","pred":"pobj","subj":"T413","obj":"T409"},{"id":"R334","pred":"punct","subj":"T414","obj":"T403"},{"id":"R335","pred":"nsubj","subj":"T415","obj":"T416"},{"id":"R336","pred":"ccomp","subj":"T416","obj":"T443"},{"id":"R337","pred":"det","subj":"T417","obj":"T420"},{"id":"R338","pred":"amod","subj":"T418","obj":"T420"},{"id":"R339","pred":"compound","subj":"T419","obj":"T420"},{"id":"R340","pred":"attr","subj":"T420","obj":"T416"},{"id":"R341","pred":"prep","subj":"T421","obj":"T420"},{"id":"R342","pred":"amod","subj":"T422","obj":"T430"},{"id":"R343","pred":"punct","subj":"T423","obj":"T422"},{"id":"R344","pred":"conj","subj":"T424","obj":"T422"},{"id":"R345","pred":"punct","subj":"T425","obj":"T426"},{"id":"R346","pred":"appos","subj":"T426","obj":"T424"},{"id":"R347","pred":"punct","subj":"T427","obj":"T426"},{"id":"R348","pred":"cc","subj":"T428","obj":"T424"},{"id":"R349","pred":"conj","subj":"T429","obj":"T424"},{"id":"R350","pred":"pobj","subj":"T430","obj":"T421"},{"id":"R351","pred":"punct","subj":"T431","obj":"T432"},{"id":"R352","pred":"appos","subj":"T432","obj":"T430"},{"id":"R353","pred":"punct","subj":"T433","obj":"T430"},{"id":"R354","pred":"conj","subj":"T434","obj":"T420"},{"id":"R355","pred":"punct","subj":"T435","obj":"T443"},{"id":"R356","pred":"advmod","subj":"T436","obj":"T443"},{"id":"R357","pred":"punct","subj":"T437","obj":"T443"},{"id":"R358","pred":"det","subj":"T438","obj":"T439"},{"id":"R359","pred":"nsubj","subj":"T439","obj":"T443"},{"id":"R360","pred":"acl","subj":"T440","obj":"T439"},{"id":"R361","pred":"poss","subj":"T441","obj":"T442"},{"id":"R362","pred":"dobj","subj":"T442","obj":"T440"},{"id":"R363","pred":"ROOT","subj":"T443","obj":"T443"},{"id":"R364","pred":"advmod","subj":"T444","obj":"T446"},{"id":"R365","pred":"advmod","subj":"T445","obj":"T446"},{"id":"R366","pred":"acomp","subj":"T446","obj":"T443"},{"id":"R367","pred":"punct","subj":"T447","obj":"T443"},{"id":"R368","pred":"nsubj","subj":"T448","obj":"T449"},{"id":"R369","pred":"ROOT","subj":"T449","obj":"T449"},{"id":"R370","pred":"det","subj":"T450","obj":"T451"},{"id":"R371","pred":"amod","subj":"T451","obj":"T454"},{"id":"R372","pred":"amod","subj":"T452","obj":"T454"},{"id":"R373","pred":"compound","subj":"T453","obj":"T454"},{"id":"R374","pred":"dobj","subj":"T454","obj":"T449"},{"id":"R375","pred":"punct","subj":"T455","obj":"T454"},{"id":"R376","pred":"nsubjpass","subj":"T456","obj":"T458"},{"id":"R377","pred":"auxpass","subj":"T457","obj":"T458"}],"text":"Transcription factors act in concert to induce lineage commitment towards Th1, Th2, or T regulatory (Treg) cells, and their counter-regulatory mechanisms were shown to be critical for polarization between Th1 and Th2 phenotypes. FOXP3 is an essential transcription factor for natural, thymus-derived (nTreg) and inducible Treg (iTreg) commitment; however, the mechanisms regulating its expression are as yet unknown. We describe a mechanism controlling iTreg polarization, which is overruled by the Th2 differentiation pathway. We demonstrated that interleukin 4 (IL-4) present at the time of T cell priming inhibits FOXP3. This inhibitory mechanism was also confirmed in Th2 cells and in T cells of transgenic mice overexpressing GATA-3 in T cells, which are shown to be deficient in transforming growth factor (TGF)-β–mediated FOXP3 induction. This inhibition is mediated by direct binding of GATA3 to the FOXP3 promoter, which represses its transactivation process. Therefore, this study provides a new understanding of tolerance development, controlled by a type 2 immune response. IL-4 treatment in mice reduces iTreg cell frequency, highlighting that therapeutic approaches that target IL-4 or GATA3 might provide new preventive strategies facilitating tolerance induction particularly in Th2-mediated diseases, such as allergy.\n"}

{"project":"UBERON-AE","denotations":[{"id":"T57","span":{"begin":285,"end":291},"obj":"http://purl.obolibrary.org/obo/UBERON_0002370"}],"text":"Transcription factors act in concert to induce lineage commitment towards Th1, Th2, or T regulatory (Treg) cells, and their counter-regulatory mechanisms were shown to be critical for polarization between Th1 and Th2 phenotypes. FOXP3 is an essential transcription factor for natural, thymus-derived (nTreg) and inducible Treg (iTreg) commitment; however, the mechanisms regulating its expression are as yet unknown. We describe a mechanism controlling iTreg polarization, which is overruled by the Th2 differentiation pathway. We demonstrated that interleukin 4 (IL-4) present at the time of T cell priming inhibits FOXP3. This inhibitory mechanism was also confirmed in Th2 cells and in T cells of transgenic mice overexpressing GATA-3 in T cells, which are shown to be deficient in transforming growth factor (TGF)-β–mediated FOXP3 induction. This inhibition is mediated by direct binding of GATA3 to the FOXP3 promoter, which represses its transactivation process. Therefore, this study provides a new understanding of tolerance development, controlled by a type 2 immune response. IL-4 treatment in mice reduces iTreg cell frequency, highlighting that therapeutic approaches that target IL-4 or GATA3 might provide new preventive strategies facilitating tolerance induction particularly in Th2-mediated diseases, such as allergy.\n"}

{"project":"GO-BP","denotations":[{"id":"T68","span":{"begin":0,"end":13},"obj":"http://purl.obolibrary.org/obo/GO_0006351"},{"id":"T69","span":{"begin":251,"end":264},"obj":"http://purl.obolibrary.org/obo/GO_0006351"},{"id":"T70","span":{"begin":798,"end":804},"obj":"http://purl.obolibrary.org/obo/GO_0040007"},{"id":"T71","span":{"begin":944,"end":959},"obj":"http://purl.obolibrary.org/obo/GO_2000144"},{"id":"T72","span":{"begin":1033,"end":1044},"obj":"http://purl.obolibrary.org/obo/GO_0032502"},{"id":"T73","span":{"begin":1069,"end":1084},"obj":"http://purl.obolibrary.org/obo/GO_0006955"},{"id":"T74","span":{"begin":1076,"end":1090},"obj":"http://purl.obolibrary.org/obo/GO_0071353"},{"id":"T75","span":{"begin":1076,"end":1090},"obj":"http://purl.obolibrary.org/obo/GO_0070670"},{"id":"T76","span":{"begin":1259,"end":1278},"obj":"http://purl.obolibrary.org/obo/GO_0002507"}],"text":"Transcription factors act in concert to induce lineage commitment towards Th1, Th2, or T regulatory (Treg) cells, and their counter-regulatory mechanisms were shown to be critical for polarization between Th1 and Th2 phenotypes. FOXP3 is an essential transcription factor for natural, thymus-derived (nTreg) and inducible Treg (iTreg) commitment; however, the mechanisms regulating its expression are as yet unknown. We describe a mechanism controlling iTreg polarization, which is overruled by the Th2 differentiation pathway. We demonstrated that interleukin 4 (IL-4) present at the time of T cell priming inhibits FOXP3. This inhibitory mechanism was also confirmed in Th2 cells and in T cells of transgenic mice overexpressing GATA-3 in T cells, which are shown to be deficient in transforming growth factor (TGF)-β–mediated FOXP3 induction. This inhibition is mediated by direct binding of GATA3 to the FOXP3 promoter, which represses its transactivation process. Therefore, this study provides a new understanding of tolerance development, controlled by a type 2 immune response. IL-4 treatment in mice reduces iTreg cell frequency, highlighting that therapeutic approaches that target IL-4 or GATA3 might provide new preventive strategies facilitating tolerance induction particularly in Th2-mediated diseases, such as allergy.\n"}

{"project":"GO-MF","denotations":[{"id":"T631","span":{"begin":561,"end":566},"obj":"http://purl.obolibrary.org/obo/GO_0005136"},{"id":"T632","span":{"begin":1086,"end":1090},"obj":"http://purl.obolibrary.org/obo/GO_0005136"},{"id":"T633","span":{"begin":1192,"end":1196},"obj":"http://purl.obolibrary.org/obo/GO_0005136"},{"id":"T634","span":{"begin":884,"end":891},"obj":"http://purl.obolibrary.org/obo/GO_0005488"}],"text":"Transcription factors act in concert to induce lineage commitment towards Th1, Th2, or T regulatory (Treg) cells, and their counter-regulatory mechanisms were shown to be critical for polarization between Th1 and Th2 phenotypes. FOXP3 is an essential transcription factor for natural, thymus-derived (nTreg) and inducible Treg (iTreg) commitment; however, the mechanisms regulating its expression are as yet unknown. We describe a mechanism controlling iTreg polarization, which is overruled by the Th2 differentiation pathway. We demonstrated that interleukin 4 (IL-4) present at the time of T cell priming inhibits FOXP3. This inhibitory mechanism was also confirmed in Th2 cells and in T cells of transgenic mice overexpressing GATA-3 in T cells, which are shown to be deficient in transforming growth factor (TGF)-β–mediated FOXP3 induction. This inhibition is mediated by direct binding of GATA3 to the FOXP3 promoter, which represses its transactivation process. Therefore, this study provides a new understanding of tolerance development, controlled by a type 2 immune response. IL-4 treatment in mice reduces iTreg cell frequency, highlighting that therapeutic approaches that target IL-4 or GATA3 might provide new preventive strategies facilitating tolerance induction particularly in Th2-mediated diseases, such as allergy.\n"}

{"project":"GO-CC","denotations":[{"id":"T635","span":{"begin":107,"end":112},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T636","span":{"begin":676,"end":681},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T637","span":{"begin":691,"end":696},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T638","span":{"begin":743,"end":748},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T639","span":{"begin":1123,"end":1127},"obj":"http://purl.obolibrary.org/obo/GO_0005623"}],"text":"Transcription factors act in concert to induce lineage commitment towards Th1, Th2, or T regulatory (Treg) cells, and their counter-regulatory mechanisms were shown to be critical for polarization between Th1 and Th2 phenotypes. FOXP3 is an essential transcription factor for natural, thymus-derived (nTreg) and inducible Treg (iTreg) commitment; however, the mechanisms regulating its expression are as yet unknown. We describe a mechanism controlling iTreg polarization, which is overruled by the Th2 differentiation pathway. We demonstrated that interleukin 4 (IL-4) present at the time of T cell priming inhibits FOXP3. This inhibitory mechanism was also confirmed in Th2 cells and in T cells of transgenic mice overexpressing GATA-3 in T cells, which are shown to be deficient in transforming growth factor (TGF)-β–mediated FOXP3 induction. This inhibition is mediated by direct binding of GATA3 to the FOXP3 promoter, which represses its transactivation process. Therefore, this study provides a new understanding of tolerance development, controlled by a type 2 immune response. IL-4 treatment in mice reduces iTreg cell frequency, highlighting that therapeutic approaches that target IL-4 or GATA3 might provide new preventive strategies facilitating tolerance induction particularly in Th2-mediated diseases, such as allergy.\n"}

{"project":"sentences","denotations":[{"id":"T59","span":{"begin":0,"end":228},"obj":"Sentence"},{"id":"T60","span":{"begin":229,"end":416},"obj":"Sentence"},{"id":"T61","span":{"begin":417,"end":527},"obj":"Sentence"},{"id":"T62","span":{"begin":528,"end":623},"obj":"Sentence"},{"id":"T63","span":{"begin":624,"end":845},"obj":"Sentence"},{"id":"T64","span":{"begin":846,"end":968},"obj":"Sentence"},{"id":"T65","span":{"begin":969,"end":1085},"obj":"Sentence"},{"id":"T66","span":{"begin":1086,"end":1334},"obj":"Sentence"},{"id":"T3","span":{"begin":0,"end":228},"obj":"Sentence"},{"id":"T4","span":{"begin":229,"end":416},"obj":"Sentence"},{"id":"T5","span":{"begin":417,"end":527},"obj":"Sentence"},{"id":"T6","span":{"begin":528,"end":623},"obj":"Sentence"},{"id":"T7","span":{"begin":624,"end":845},"obj":"Sentence"},{"id":"T8","span":{"begin":846,"end":968},"obj":"Sentence"},{"id":"T9","span":{"begin":969,"end":1085},"obj":"Sentence"},{"id":"T10","span":{"begin":1086,"end":1334},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"Transcription factors act in concert to induce lineage commitment towards Th1, Th2, or T regulatory (Treg) cells, and their counter-regulatory mechanisms were shown to be critical for polarization between Th1 and Th2 phenotypes. FOXP3 is an essential transcription factor for natural, thymus-derived (nTreg) and inducible Treg (iTreg) commitment; however, the mechanisms regulating its expression are as yet unknown. We describe a mechanism controlling iTreg polarization, which is overruled by the Th2 differentiation pathway. We demonstrated that interleukin 4 (IL-4) present at the time of T cell priming inhibits FOXP3. This inhibitory mechanism was also confirmed in Th2 cells and in T cells of transgenic mice overexpressing GATA-3 in T cells, which are shown to be deficient in transforming growth factor (TGF)-β–mediated FOXP3 induction. This inhibition is mediated by direct binding of GATA3 to the FOXP3 promoter, which represses its transactivation process. Therefore, this study provides a new understanding of tolerance development, controlled by a type 2 immune response. IL-4 treatment in mice reduces iTreg cell frequency, highlighting that therapeutic approaches that target IL-4 or GATA3 might provide new preventive strategies facilitating tolerance induction particularly in Th2-mediated diseases, such as allergy.\n"}

{"project":"ICD10","denotations":[{"id":"T630","span":{"begin":1326,"end":1333},"obj":"http://purl.bioontology.org/ontology/ICD10/T78.4"}],"text":"Transcription factors act in concert to induce lineage commitment towards Th1, Th2, or T regulatory (Treg) cells, and their counter-regulatory mechanisms were shown to be critical for polarization between Th1 and Th2 phenotypes. FOXP3 is an essential transcription factor for natural, thymus-derived (nTreg) and inducible Treg (iTreg) commitment; however, the mechanisms regulating its expression are as yet unknown. We describe a mechanism controlling iTreg polarization, which is overruled by the Th2 differentiation pathway. We demonstrated that interleukin 4 (IL-4) present at the time of T cell priming inhibits FOXP3. This inhibitory mechanism was also confirmed in Th2 cells and in T cells of transgenic mice overexpressing GATA-3 in T cells, which are shown to be deficient in transforming growth factor (TGF)-β–mediated FOXP3 induction. This inhibition is mediated by direct binding of GATA3 to the FOXP3 promoter, which represses its transactivation process. Therefore, this study provides a new understanding of tolerance development, controlled by a type 2 immune response. IL-4 treatment in mice reduces iTreg cell frequency, highlighting that therapeutic approaches that target IL-4 or GATA3 might provide new preventive strategies facilitating tolerance induction particularly in Th2-mediated diseases, such as allergy.\n"}

{"project":"events-check-again","denotations":[{"id":"T768","span":{"begin":785,"end":819},"obj":"Protein"},{"id":"T769","span":{"begin":820,"end":828},"obj":"Positive_regulation"},{"id":"T770","span":{"begin":829,"end":834},"obj":"Protein"},{"id":"T771","span":{"begin":835,"end":844},"obj":"Positive_regulation"},{"id":"T772","span":{"begin":865,"end":873},"obj":"Positive_regulation"},{"id":"T773","span":{"begin":884,"end":891},"obj":"Binding"},{"id":"T774","span":{"begin":895,"end":900},"obj":"Protein"},{"id":"T775","span":{"begin":908,"end":913},"obj":"Protein"},{"id":"T776","span":{"begin":914,"end":922},"obj":"Entity"},{"id":"T777","span":{"begin":1086,"end":1090},"obj":"Protein"},{"id":"T778","span":{"begin":1185,"end":1191},"obj":"Regulation"},{"id":"T779","span":{"begin":1185,"end":1191},"obj":"Regulation"},{"id":"T780","span":{"begin":1192,"end":1196},"obj":"Protein"},{"id":"T781","span":{"begin":1200,"end":1205},"obj":"Protein"},{"id":"T758","span":{"begin":229,"end":234},"obj":"Protein"},{"id":"T759","span":{"begin":371,"end":381},"obj":"Regulation"},{"id":"T760","span":{"begin":386,"end":396},"obj":"Gene_expression"},{"id":"T761","span":{"begin":549,"end":562},"obj":"Protein"},{"id":"T762","span":{"begin":564,"end":568},"obj":"Protein"},{"id":"T763","span":{"begin":608,"end":616},"obj":"Negative_regulation"},{"id":"T764","span":{"begin":617,"end":622},"obj":"Protein"},{"id":"T765","span":{"begin":716,"end":730},"obj":"Gene_expression"},{"id":"T766","span":{"begin":731,"end":737},"obj":"Protein"},{"id":"T767","span":{"begin":772,"end":781},"obj":"Negative_regulation"}],"relations":[{"id":"R607","pred":"themeOf","subj":"T780","obj":"T778"},{"id":"R608","pred":"themeOf","subj":"T781","obj":"T779"},{"id":"R658","pred":"themeOf","subj":"T760","obj":"T759"},{"id":"R660","pred":"equivalentTo","subj":"T762","obj":"T761"},{"id":"R599","pred":"causeOf","subj":"T768","obj":"T769"},{"id":"R600","pred":"themeOf","subj":"T769","obj":"T767"},{"id":"R601","pred":"themeOf","subj":"T770","obj":"T771"},{"id":"R602","pred":"themeOf","subj":"T771","obj":"T769"},{"id":"R603","pred":"causeOf","subj":"T773","obj":"T772"},{"id":"R604","pred":"themeOf","subj":"T774","obj":"T773"},{"id":"R605","pred":"themeOf","subj":"T776","obj":"T773"},{"id":"R606","pred":"partOf","subj":"T776","obj":"T775"},{"id":"R657","pred":"themeOf","subj":"T758","obj":"T760"},{"id":"R659","pred":"causeOf","subj":"T761","obj":"T763"},{"id":"R661","pred":"themeOf","subj":"T764","obj":"T763"},{"id":"R662","pred":"themeOf","subj":"T766","obj":"T765"},{"id":"R663","pred":"themeOf","subj":"T767","obj":"T772"}],"attributes":[{"id":"M7","pred":"Speculation","subj":"T759","obj":"true"}],"text":"Transcription factors act in concert to induce lineage commitment towards Th1, Th2, or T regulatory (Treg) cells, and their counter-regulatory mechanisms were shown to be critical for polarization between Th1 and Th2 phenotypes. FOXP3 is an essential transcription factor for natural, thymus-derived (nTreg) and inducible Treg (iTreg) commitment; however, the mechanisms regulating its expression are as yet unknown. We describe a mechanism controlling iTreg polarization, which is overruled by the Th2 differentiation pathway. We demonstrated that interleukin 4 (IL-4) present at the time of T cell priming inhibits FOXP3. This inhibitory mechanism was also confirmed in Th2 cells and in T cells of transgenic mice overexpressing GATA-3 in T cells, which are shown to be deficient in transforming growth factor (TGF)-β–mediated FOXP3 induction. This inhibition is mediated by direct binding of GATA3 to the FOXP3 promoter, which represses its transactivation process. Therefore, this study provides a new understanding of tolerance development, controlled by a type 2 immune response. IL-4 treatment in mice reduces iTreg cell frequency, highlighting that therapeutic approaches that target IL-4 or GATA3 might provide new preventive strategies facilitating tolerance induction particularly in Th2-mediated diseases, such as allergy.\n"}

{"project":"bionlp-st-ge-2016-reference-tees","denotations":[{"id":"T647","span":{"begin":205,"end":208},"obj":"Protein"},{"id":"T648","span":{"begin":213,"end":227},"obj":"Protein"},{"id":"T649","span":{"begin":229,"end":234},"obj":"Protein"},{"id":"T650","span":{"begin":386,"end":396},"obj":"Gene_expression"},{"id":"T651","span":{"begin":371,"end":381},"obj":"Regulation"},{"id":"T652","span":{"begin":549,"end":562},"obj":"Protein"},{"id":"T653","span":{"begin":564,"end":568},"obj":"Protein"},{"id":"T654","span":{"begin":617,"end":622},"obj":"Protein"},{"id":"T655","span":{"begin":608,"end":616},"obj":"Negative_regulation"},{"id":"T656","span":{"begin":608,"end":616},"obj":"Negative_regulation"},{"id":"T657","span":{"begin":731,"end":737},"obj":"Protein"},{"id":"T658","span":{"begin":829,"end":834},"obj":"Protein"},{"id":"T659","span":{"begin":716,"end":730},"obj":"Gene_expression"},{"id":"T660","span":{"begin":835,"end":844},"obj":"Positive_regulation"},{"id":"T661","span":{"begin":772,"end":781},"obj":"Negative_regulation"},{"id":"T662","span":{"begin":895,"end":900},"obj":"Protein"},{"id":"T663","span":{"begin":908,"end":922},"obj":"Protein"},{"id":"T664","span":{"begin":884,"end":891},"obj":"Binding"},{"id":"T665","span":{"begin":884,"end":891},"obj":"Binding"},{"id":"T666","span":{"begin":1086,"end":1090},"obj":"Protein"},{"id":"T667","span":{"begin":1185,"end":1196},"obj":"Protein"},{"id":"T668","span":{"begin":1200,"end":1205},"obj":"Protein"}],"relations":[{"id":"R555","pred":"themeOf","subj":"T662","obj":"T665"},{"id":"R556","pred":"themeOf","subj":"T663","obj":"T665"},{"id":"R545","pred":"themeOf","subj":"T649","obj":"T650"},{"id":"R546","pred":"themeOf","subj":"T650","obj":"T651"},{"id":"R547","pred":"causeOf","subj":"T652","obj":"T655"},{"id":"R548","pred":"causeOf","subj":"T653","obj":"T656"},{"id":"R549","pred":"themeOf","subj":"T654","obj":"T655"},{"id":"R550","pred":"themeOf","subj":"T654","obj":"T656"},{"id":"R551","pred":"themeOf","subj":"T657","obj":"T659"},{"id":"R552","pred":"themeOf","subj":"T658","obj":"T660"},{"id":"R553","pred":"themeOf","subj":"T660","obj":"T661"},{"id":"R554","pred":"themeOf","subj":"T662","obj":"T664"}],"text":"Transcription factors act in concert to induce lineage commitment towards Th1, Th2, or T regulatory (Treg) cells, and their counter-regulatory mechanisms were shown to be critical for polarization between Th1 and Th2 phenotypes. FOXP3 is an essential transcription factor for natural, thymus-derived (nTreg) and inducible Treg (iTreg) commitment; however, the mechanisms regulating its expression are as yet unknown. We describe a mechanism controlling iTreg polarization, which is overruled by the Th2 differentiation pathway. We demonstrated that interleukin 4 (IL-4) present at the time of T cell priming inhibits FOXP3. This inhibitory mechanism was also confirmed in Th2 cells and in T cells of transgenic mice overexpressing GATA-3 in T cells, which are shown to be deficient in transforming growth factor (TGF)-β–mediated FOXP3 induction. This inhibition is mediated by direct binding of GATA3 to the FOXP3 promoter, which represses its transactivation process. Therefore, this study provides a new understanding of tolerance development, controlled by a type 2 immune response. IL-4 treatment in mice reduces iTreg cell frequency, highlighting that therapeutic approaches that target IL-4 or GATA3 might provide new preventive strategies facilitating tolerance induction particularly in Th2-mediated diseases, such as allergy.\n"}

{"project":"bionlp-st-ge-2016-reference","denotations":[{"id":"T102","span":{"begin":549,"end":562},"obj":"Protein"},{"id":"T103","span":{"begin":564,"end":568},"obj":"Protein"},{"id":"T104","span":{"begin":617,"end":622},"obj":"Protein"},{"id":"T105","span":{"begin":731,"end":737},"obj":"Protein"},{"id":"T106","span":{"begin":785,"end":819},"obj":"Protein"},{"id":"T78","span":{"begin":835,"end":844},"obj":"Positive_regulation"},{"id":"T79","span":{"begin":865,"end":873},"obj":"Positive_regulation"},{"id":"T80","span":{"begin":884,"end":891},"obj":"Binding"},{"id":"T81","span":{"begin":1185,"end":1191},"obj":"Regulation"},{"id":"T82","span":{"begin":1185,"end":1191},"obj":"Regulation"},{"id":"T85","span":{"begin":371,"end":381},"obj":"Regulation"},{"id":"T86","span":{"begin":386,"end":396},"obj":"Gene_expression"},{"id":"T87","span":{"begin":608,"end":616},"obj":"Negative_regulation"},{"id":"T88","span":{"begin":716,"end":730},"obj":"Gene_expression"},{"id":"T89","span":{"begin":772,"end":781},"obj":"Negative_regulation"},{"id":"T90","span":{"begin":820,"end":828},"obj":"Positive_regulation"},{"id":"T92","span":{"begin":829,"end":834},"obj":"Protein"},{"id":"T93","span":{"begin":895,"end":900},"obj":"Protein"},{"id":"T94","span":{"begin":908,"end":913},"obj":"Protein"},{"id":"T95","span":{"begin":1086,"end":1090},"obj":"Protein"},{"id":"T96","span":{"begin":1192,"end":1196},"obj":"Protein"},{"id":"T97","span":{"begin":1200,"end":1205},"obj":"Protein"},{"id":"T100","span":{"begin":914,"end":922},"obj":"Entity"},{"id":"T101","span":{"begin":229,"end":234},"obj":"Protein"}],"relations":[{"id":"R622","pred":"themeOf","subj":"T86","obj":"T85"},{"id":"R623","pred":"themeOf","subj":"T89","obj":"T79"},{"id":"R624","pred":"themeOf","subj":"T90","obj":"T89"},{"id":"R625","pred":"themeOf","subj":"T92","obj":"T78"},{"id":"R626","pred":"themeOf","subj":"T93","obj":"T80"},{"id":"R627","pred":"themeOf","subj":"T96","obj":"T81"},{"id":"R628","pred":"themeOf","subj":"T97","obj":"T82"},{"id":"R631","pred":"themeOf","subj":"T100","obj":"T80"},{"id":"R632","pred":"partOf","subj":"T100","obj":"T94"},{"id":"R633","pred":"themeOf","subj":"T101","obj":"T86"},{"id":"R39","pred":"causeOf","subj":"T102","obj":"T87"},{"id":"R40","pred":"equivalentTo","subj":"T103","obj":"T102"},{"id":"R41","pred":"themeOf","subj":"T104","obj":"T87"},{"id":"R42","pred":"themeOf","subj":"T105","obj":"T88"},{"id":"R43","pred":"causeOf","subj":"T106","obj":"T90"},{"id":"R618","pred":"themeOf","subj":"T78","obj":"T90"},{"id":"R619","pred":"causeOf","subj":"T80","obj":"T79"}],"attributes":[{"id":"M6","pred":"Speculation","subj":"T85","obj":"true"}],"namespaces":[{"prefix":"_base","uri":"http://bionlp.dbcls.jp/ontology/ge.owl#"}],"text":"Transcription factors act in concert to induce lineage commitment towards Th1, Th2, or T regulatory (Treg) cells, and their counter-regulatory mechanisms were shown to be critical for polarization between Th1 and Th2 phenotypes. FOXP3 is an essential transcription factor for natural, thymus-derived (nTreg) and inducible Treg (iTreg) commitment; however, the mechanisms regulating its expression are as yet unknown. We describe a mechanism controlling iTreg polarization, which is overruled by the Th2 differentiation pathway. We demonstrated that interleukin 4 (IL-4) present at the time of T cell priming inhibits FOXP3. This inhibitory mechanism was also confirmed in Th2 cells and in T cells of transgenic mice overexpressing GATA-3 in T cells, which are shown to be deficient in transforming growth factor (TGF)-β–mediated FOXP3 induction. This inhibition is mediated by direct binding of GATA3 to the FOXP3 promoter, which represses its transactivation process. Therefore, this study provides a new understanding of tolerance development, controlled by a type 2 immune response. IL-4 treatment in mice reduces iTreg cell frequency, highlighting that therapeutic approaches that target IL-4 or GATA3 might provide new preventive strategies facilitating tolerance induction particularly in Th2-mediated diseases, such as allergy.\n"}

{"project":"bionlp-st-ge-2016-uniprot","denotations":[{"id":"T341","span":{"begin":229,"end":234},"obj":"Q9BZS1"},{"id":"T342","span":{"begin":549,"end":562},"obj":"P05112"},{"id":"T343","span":{"begin":564,"end":568},"obj":"P05112"},{"id":"T344","span":{"begin":617,"end":622},"obj":"Q9BZS1"},{"id":"T345","span":{"begin":731,"end":737},"obj":"P23771"},{"id":"T346","span":{"begin":829,"end":834},"obj":"Q9BZS1"},{"id":"T347","span":{"begin":895,"end":900},"obj":"P23771"},{"id":"T348","span":{"begin":908,"end":913},"obj":"Q9BZS1"},{"id":"T349","span":{"begin":1086,"end":1090},"obj":"P05112"},{"id":"T350","span":{"begin":1192,"end":1196},"obj":"P05112"},{"id":"T351","span":{"begin":1200,"end":1205},"obj":"P23771"}],"namespaces":[{"prefix":"_base","uri":"http://www.uniprot.org/uniprot/"}],"text":"Transcription factors act in concert to induce lineage commitment towards Th1, Th2, or T regulatory (Treg) cells, and their counter-regulatory mechanisms were shown to be critical for polarization between Th1 and Th2 phenotypes. FOXP3 is an essential transcription factor for natural, thymus-derived (nTreg) and inducible Treg (iTreg) commitment; however, the mechanisms regulating its expression are as yet unknown. We describe a mechanism controlling iTreg polarization, which is overruled by the Th2 differentiation pathway. We demonstrated that interleukin 4 (IL-4) present at the time of T cell priming inhibits FOXP3. This inhibitory mechanism was also confirmed in Th2 cells and in T cells of transgenic mice overexpressing GATA-3 in T cells, which are shown to be deficient in transforming growth factor (TGF)-β–mediated FOXP3 induction. This inhibition is mediated by direct binding of GATA3 to the FOXP3 promoter, which represses its transactivation process. Therefore, this study provides a new understanding of tolerance development, controlled by a type 2 immune response. IL-4 treatment in mice reduces iTreg cell frequency, highlighting that therapeutic approaches that target IL-4 or GATA3 might provide new preventive strategies facilitating tolerance induction particularly in Th2-mediated diseases, such as allergy.\n"}

{"project":"test2","denotations":[{"id":"T37","span":{"begin":229,"end":234},"obj":"Protein"},{"id":"T38","span":{"begin":549,"end":562},"obj":"Protein"},{"id":"T39","span":{"begin":564,"end":568},"obj":"Protein"},{"id":"T40","span":{"begin":608,"end":616},"obj":"Negative_regulation"},{"id":"T41","span":{"begin":617,"end":622},"obj":"Protein"},{"id":"T42","span":{"begin":716,"end":730},"obj":"Gene_expression"},{"id":"T43","span":{"begin":731,"end":737},"obj":"Protein"},{"id":"T44","span":{"begin":772,"end":781},"obj":"Negative_regulation"},{"id":"T45","span":{"begin":785,"end":819},"obj":"Protein"},{"id":"T46","span":{"begin":820,"end":828},"obj":"Positive_regulation"},{"id":"T47","span":{"begin":829,"end":834},"obj":"Protein"},{"id":"T48","span":{"begin":835,"end":844},"obj":"Positive_regulation"},{"id":"T49","span":{"begin":884,"end":891},"obj":"Binding"},{"id":"T50","span":{"begin":895,"end":900},"obj":"Protein"},{"id":"T51","span":{"begin":908,"end":913},"obj":"Protein"},{"id":"T52","span":{"begin":914,"end":922},"obj":"Entity"},{"id":"T53","span":{"begin":1086,"end":1090},"obj":"Protein"},{"id":"T54","span":{"begin":1185,"end":1191},"obj":"Binding"},{"id":"T55","span":{"begin":1192,"end":1196},"obj":"Protein"},{"id":"T56","span":{"begin":1200,"end":1205},"obj":"Protein"}],"relations":[{"id":"R27","pred":"causeOf","subj":"T38","obj":"T40"},{"id":"R28","pred":"equivalentTo","subj":"T39","obj":"T38"},{"id":"R29","pred":"themeOf","subj":"T41","obj":"T40"},{"id":"R30","pred":"themeOf","subj":"T43","obj":"T42"},{"id":"R31","pred":"themeOf","subj":"T47","obj":"T48"},{"id":"R32","pred":"themeOf","subj":"T48","obj":"T46"},{"id":"R33","pred":"themeOf","subj":"T50","obj":"T49"},{"id":"R34","pred":"partOf","subj":"T52","obj":"T51"},{"id":"R35","pred":"themeOf","subj":"T52","obj":"T49"},{"id":"R36","pred":"themeOf","subj":"T53","obj":"T54"},{"id":"R37","pred":"themeOf","subj":"T55","obj":"T54"},{"id":"R38","pred":"themeOf","subj":"T56","obj":"T54"}],"text":"Transcription factors act in concert to induce lineage commitment towards Th1, Th2, or T regulatory (Treg) cells, and their counter-regulatory mechanisms were shown to be critical for polarization between Th1 and Th2 phenotypes. FOXP3 is an essential transcription factor for natural, thymus-derived (nTreg) and inducible Treg (iTreg) commitment; however, the mechanisms regulating its expression are as yet unknown. We describe a mechanism controlling iTreg polarization, which is overruled by the Th2 differentiation pathway. We demonstrated that interleukin 4 (IL-4) present at the time of T cell priming inhibits FOXP3. This inhibitory mechanism was also confirmed in Th2 cells and in T cells of transgenic mice overexpressing GATA-3 in T cells, which are shown to be deficient in transforming growth factor (TGF)-β–mediated FOXP3 induction. This inhibition is mediated by direct binding of GATA3 to the FOXP3 promoter, which represses its transactivation process. Therefore, this study provides a new understanding of tolerance development, controlled by a type 2 immune response. IL-4 treatment in mice reduces iTreg cell frequency, highlighting that therapeutic approaches that target IL-4 or GATA3 might provide new preventive strategies facilitating tolerance induction particularly in Th2-mediated diseases, such as allergy.\n"}