PMC:2222968 / 17545-20240 JSON TXT

Annnotations TAB JSON ListView MergeView

2_test

{"project":"2_test","denotations":[{"id":"18162042-11483607-84705019","span":{"begin":2025,"end":2027},"obj":"11483607"},{"id":"T41406","span":{"begin":2025,"end":2027},"obj":"11483607"}],"text":"The Role of TGF-β in T Cell Differentiation\nAlthough TGF-β–reduced CD25, IL-4 expression, and CD25 expression (Figure 6B), IL-4 significantly inhibited TGF-β–mediated induction of FOXP3 in naive T cells driven toward FOXP3+ T cells, as shown by FACS analysis (Figure 6A). It is known that IL-4 is a potent growth factor and may therefore favor the proliferation of FOXP3– cells and thus decrease the relative percentage of FOXP3+ cells. However, analysis of cell division kinetics by CFSE-labeling demonstrated that IL-4 did not differentially promote cell growth of FOXP3+ over that of FOXP3–. In fact both populations showed similarly enhanced proliferation (Figure 6A). Furthermore the TGF-β–mediated induction of FOXP3 expression was not caused by overgrowth of a CD25–FOXP3+ minority, since the number of FOXP3+ cells was low/absent in the purified CD4+CD45RA+ T cells (between 0% and 1%), and the FOXP3+ cells were not confined to the highly divided cells. CD25 was down-regulated in TGF-β–treated cells compare to activated T cells, which was even more pronounced in cells cultured with TGF-β and IL-4.\nFigure 6 IL-4 Inhibits TGF-β–Mediated iTreg Commitment\nCFSE-labeled CD4+CD45RA+ cells were activated with plate-bound anti-CD3/CD28, TGF-β, and IL-4, as indicated. After 5 d, cells were analyzed by flow cytometry (A) and results of six independent experiments are shown in the bar graph below (B). Statistical significance (one-way Anova, Newman-Keuls) is indicated by asterisks (**p ≤ 0.01, ***p ≤ 0.001). (C) Kinetic analysis of intracellular GATA3 and FOXP3 staining is shown in panel C following exposure of CD4+CD45RA+ T cells to anti-CD3/28, IL-4 and TGF-β. Data are representative of three independent experiments. The addition of IL-4 to iTreg-driving conditions decreased the number of FOXP3+ cells (Figure 6B). In line with the previous findings, the IL-4–producing cells and the FOXP3 expressing cells are nonoverlapping populations. Since FOXP3 is known to act as a repressor of cytokine expression [20], we therefore analyzed GATA3 and FOXP3 expression. The expression kinetic of naive T cells exposed to IL-4 and TGF-β demonstrated that GATA3 and FOXP3 are initially found in separate populations (day 2), but transiently co-express both factors (days 4–8), before establishing separate populations at the end of the differentiation process (day 10; Figure 6C), suggesting that GATA3 inhibits the development of iTreg cells by repressing FOXP3.\nThese results showed that IL-4 acts in vitro as an inhibitor of FOXP3 expression, without interfering with TGF-β signaling, probably acting at the level of transcription factors, and possibly by a GATA3-dependent mechanism."}

pmc-enju-pas

bionlp-st-ge-2016-coref

{"project":"bionlp-st-ge-2016-coref","denotations":[{"id":"T8704","span":{"begin":2260,"end":2272},"obj":"Anaphor"},{"id":"T8705","span":{"begin":2164,"end":2169},"obj":"Antecedent"},{"id":"T8706","span":{"begin":2174,"end":2179},"obj":"Antecedent"}],"relations":[{"id":"R6681","pred":"boundBy","subj":"T8704","obj":"T8705"},{"id":"R6682","pred":"boundBy","subj":"T8704","obj":"T8706"}],"namespaces":[{"prefix":"_base","uri":"https://bionlp.dbcls.jp/ontology/ge.owl#"}],"text":"The Role of TGF-β in T Cell Differentiation\nAlthough TGF-β–reduced CD25, IL-4 expression, and CD25 expression (Figure 6B), IL-4 significantly inhibited TGF-β–mediated induction of FOXP3 in naive T cells driven toward FOXP3+ T cells, as shown by FACS analysis (Figure 6A). It is known that IL-4 is a potent growth factor and may therefore favor the proliferation of FOXP3– cells and thus decrease the relative percentage of FOXP3+ cells. However, analysis of cell division kinetics by CFSE-labeling demonstrated that IL-4 did not differentially promote cell growth of FOXP3+ over that of FOXP3–. In fact both populations showed similarly enhanced proliferation (Figure 6A). Furthermore the TGF-β–mediated induction of FOXP3 expression was not caused by overgrowth of a CD25–FOXP3+ minority, since the number of FOXP3+ cells was low/absent in the purified CD4+CD45RA+ T cells (between 0% and 1%), and the FOXP3+ cells were not confined to the highly divided cells. CD25 was down-regulated in TGF-β–treated cells compare to activated T cells, which was even more pronounced in cells cultured with TGF-β and IL-4.\nFigure 6 IL-4 Inhibits TGF-β–Mediated iTreg Commitment\nCFSE-labeled CD4+CD45RA+ cells were activated with plate-bound anti-CD3/CD28, TGF-β, and IL-4, as indicated. After 5 d, cells were analyzed by flow cytometry (A) and results of six independent experiments are shown in the bar graph below (B). Statistical significance (one-way Anova, Newman-Keuls) is indicated by asterisks (**p ≤ 0.01, ***p ≤ 0.001). (C) Kinetic analysis of intracellular GATA3 and FOXP3 staining is shown in panel C following exposure of CD4+CD45RA+ T cells to anti-CD3/28, IL-4 and TGF-β. Data are representative of three independent experiments. The addition of IL-4 to iTreg-driving conditions decreased the number of FOXP3+ cells (Figure 6B). In line with the previous findings, the IL-4–producing cells and the FOXP3 expressing cells are nonoverlapping populations. Since FOXP3 is known to act as a repressor of cytokine expression [20], we therefore analyzed GATA3 and FOXP3 expression. The expression kinetic of naive T cells exposed to IL-4 and TGF-β demonstrated that GATA3 and FOXP3 are initially found in separate populations (day 2), but transiently co-express both factors (days 4–8), before establishing separate populations at the end of the differentiation process (day 10; Figure 6C), suggesting that GATA3 inhibits the development of iTreg cells by repressing FOXP3.\nThese results showed that IL-4 acts in vitro as an inhibitor of FOXP3 expression, without interfering with TGF-β signaling, probably acting at the level of transcription factors, and possibly by a GATA3-dependent mechanism."}

bionlp-st-ge-2016-spacy-parsed

GO-BP

{"project":"GO-BP","denotations":[{"id":"T8273","span":{"begin":306,"end":312},"obj":"http://purl.obolibrary.org/obo/GO_0040007"},{"id":"T8274","span":{"begin":557,"end":563},"obj":"http://purl.obolibrary.org/obo/GO_0040007"},{"id":"T8275","span":{"begin":458,"end":471},"obj":"http://purl.obolibrary.org/obo/GO_0051301"},{"id":"T8276","span":{"begin":552,"end":563},"obj":"http://purl.obolibrary.org/obo/GO_0016049"},{"id":"T8277","span":{"begin":2424,"end":2435},"obj":"http://purl.obolibrary.org/obo/GO_0032502"},{"id":"T8278","span":{"begin":2585,"end":2594},"obj":"http://purl.obolibrary.org/obo/GO_0023052"},{"id":"T8279","span":{"begin":2628,"end":2641},"obj":"http://purl.obolibrary.org/obo/GO_0006351"}],"text":"The Role of TGF-β in T Cell Differentiation\nAlthough TGF-β–reduced CD25, IL-4 expression, and CD25 expression (Figure 6B), IL-4 significantly inhibited TGF-β–mediated induction of FOXP3 in naive T cells driven toward FOXP3+ T cells, as shown by FACS analysis (Figure 6A). It is known that IL-4 is a potent growth factor and may therefore favor the proliferation of FOXP3– cells and thus decrease the relative percentage of FOXP3+ cells. However, analysis of cell division kinetics by CFSE-labeling demonstrated that IL-4 did not differentially promote cell growth of FOXP3+ over that of FOXP3–. In fact both populations showed similarly enhanced proliferation (Figure 6A). Furthermore the TGF-β–mediated induction of FOXP3 expression was not caused by overgrowth of a CD25–FOXP3+ minority, since the number of FOXP3+ cells was low/absent in the purified CD4+CD45RA+ T cells (between 0% and 1%), and the FOXP3+ cells were not confined to the highly divided cells. CD25 was down-regulated in TGF-β–treated cells compare to activated T cells, which was even more pronounced in cells cultured with TGF-β and IL-4.\nFigure 6 IL-4 Inhibits TGF-β–Mediated iTreg Commitment\nCFSE-labeled CD4+CD45RA+ cells were activated with plate-bound anti-CD3/CD28, TGF-β, and IL-4, as indicated. After 5 d, cells were analyzed by flow cytometry (A) and results of six independent experiments are shown in the bar graph below (B). Statistical significance (one-way Anova, Newman-Keuls) is indicated by asterisks (**p ≤ 0.01, ***p ≤ 0.001). (C) Kinetic analysis of intracellular GATA3 and FOXP3 staining is shown in panel C following exposure of CD4+CD45RA+ T cells to anti-CD3/28, IL-4 and TGF-β. Data are representative of three independent experiments. The addition of IL-4 to iTreg-driving conditions decreased the number of FOXP3+ cells (Figure 6B). In line with the previous findings, the IL-4–producing cells and the FOXP3 expressing cells are nonoverlapping populations. Since FOXP3 is known to act as a repressor of cytokine expression [20], we therefore analyzed GATA3 and FOXP3 expression. The expression kinetic of naive T cells exposed to IL-4 and TGF-β demonstrated that GATA3 and FOXP3 are initially found in separate populations (day 2), but transiently co-express both factors (days 4–8), before establishing separate populations at the end of the differentiation process (day 10; Figure 6C), suggesting that GATA3 inhibits the development of iTreg cells by repressing FOXP3.\nThese results showed that IL-4 acts in vitro as an inhibitor of FOXP3 expression, without interfering with TGF-β signaling, probably acting at the level of transcription factors, and possibly by a GATA3-dependent mechanism."}

GO-MF

{"project":"GO-MF","denotations":[{"id":"T9216","span":{"begin":73,"end":77},"obj":"http://purl.obolibrary.org/obo/GO_0005136"},{"id":"T9217","span":{"begin":123,"end":127},"obj":"http://purl.obolibrary.org/obo/GO_0005136"},{"id":"T9218","span":{"begin":289,"end":293},"obj":"http://purl.obolibrary.org/obo/GO_0005136"},{"id":"T9219","span":{"begin":516,"end":520},"obj":"http://purl.obolibrary.org/obo/GO_0005136"},{"id":"T9220","span":{"begin":1104,"end":1108},"obj":"http://purl.obolibrary.org/obo/GO_0005136"},{"id":"T9221","span":{"begin":1751,"end":1755},"obj":"http://purl.obolibrary.org/obo/GO_0005136"},{"id":"T9222","span":{"begin":1874,"end":1878},"obj":"http://purl.obolibrary.org/obo/GO_0005136"},{"id":"T9223","span":{"begin":2131,"end":2135},"obj":"http://purl.obolibrary.org/obo/GO_0005136"},{"id":"T9224","span":{"begin":2498,"end":2502},"obj":"http://purl.obolibrary.org/obo/GO_0005136"},{"id":"T26154","span":{"begin":1120,"end":1124},"obj":"http://purl.obolibrary.org/obo/GO_0005136"},{"id":"T26155","span":{"begin":1255,"end":1259},"obj":"http://purl.obolibrary.org/obo/GO_0005136"},{"id":"T26156","span":{"begin":1659,"end":1663},"obj":"http://purl.obolibrary.org/obo/GO_0005136"},{"id":"T26157","span":{"begin":1655,"end":1661},"obj":"http://purl.obolibrary.org/obo/GO_0032003"}],"text":"The Role of TGF-β in T Cell Differentiation\nAlthough TGF-β–reduced CD25, IL-4 expression, and CD25 expression (Figure 6B), IL-4 significantly inhibited TGF-β–mediated induction of FOXP3 in naive T cells driven toward FOXP3+ T cells, as shown by FACS analysis (Figure 6A). It is known that IL-4 is a potent growth factor and may therefore favor the proliferation of FOXP3– cells and thus decrease the relative percentage of FOXP3+ cells. However, analysis of cell division kinetics by CFSE-labeling demonstrated that IL-4 did not differentially promote cell growth of FOXP3+ over that of FOXP3–. In fact both populations showed similarly enhanced proliferation (Figure 6A). Furthermore the TGF-β–mediated induction of FOXP3 expression was not caused by overgrowth of a CD25–FOXP3+ minority, since the number of FOXP3+ cells was low/absent in the purified CD4+CD45RA+ T cells (between 0% and 1%), and the FOXP3+ cells were not confined to the highly divided cells. CD25 was down-regulated in TGF-β–treated cells compare to activated T cells, which was even more pronounced in cells cultured with TGF-β and IL-4.\nFigure 6 IL-4 Inhibits TGF-β–Mediated iTreg Commitment\nCFSE-labeled CD4+CD45RA+ cells were activated with plate-bound anti-CD3/CD28, TGF-β, and IL-4, as indicated. After 5 d, cells were analyzed by flow cytometry (A) and results of six independent experiments are shown in the bar graph below (B). Statistical significance (one-way Anova, Newman-Keuls) is indicated by asterisks (**p ≤ 0.01, ***p ≤ 0.001). (C) Kinetic analysis of intracellular GATA3 and FOXP3 staining is shown in panel C following exposure of CD4+CD45RA+ T cells to anti-CD3/28, IL-4 and TGF-β. Data are representative of three independent experiments. The addition of IL-4 to iTreg-driving conditions decreased the number of FOXP3+ cells (Figure 6B). In line with the previous findings, the IL-4–producing cells and the FOXP3 expressing cells are nonoverlapping populations. Since FOXP3 is known to act as a repressor of cytokine expression [20], we therefore analyzed GATA3 and FOXP3 expression. The expression kinetic of naive T cells exposed to IL-4 and TGF-β demonstrated that GATA3 and FOXP3 are initially found in separate populations (day 2), but transiently co-express both factors (days 4–8), before establishing separate populations at the end of the differentiation process (day 10; Figure 6C), suggesting that GATA3 inhibits the development of iTreg cells by repressing FOXP3.\nThese results showed that IL-4 acts in vitro as an inhibitor of FOXP3 expression, without interfering with TGF-β signaling, probably acting at the level of transcription factors, and possibly by a GATA3-dependent mechanism."}

GO-CC

sentences

events-check-again

bionlp-st-ge-2016-reference-tees

{"project":"bionlp-st-ge-2016-reference-tees","denotations":[{"id":"T26162","span":{"begin":1120,"end":1124},"obj":"Protein"},{"id":"T26163","span":{"begin":1134,"end":1165},"obj":"Protein"},{"id":"T26164","span":{"begin":1125,"end":1133},"obj":"Negative_regulation"},{"id":"T26165","span":{"begin":1179,"end":1182},"obj":"Protein"},{"id":"T26166","span":{"begin":1183,"end":1189},"obj":"Protein"},{"id":"T26167","span":{"begin":1234,"end":1237},"obj":"Protein"},{"id":"T26168","span":{"begin":1238,"end":1242},"obj":"Protein"},{"id":"T26169","span":{"begin":1244,"end":1249},"obj":"Protein"},{"id":"T26170","span":{"begin":1255,"end":1259},"obj":"Protein"},{"id":"T26171","span":{"begin":1556,"end":1561},"obj":"Protein"},{"id":"T26172","span":{"begin":1566,"end":1571},"obj":"Protein"},{"id":"T26173","span":{"begin":1623,"end":1626},"obj":"Protein"},{"id":"T26174","span":{"begin":1627,"end":1633},"obj":"Protein"},{"id":"T26175","span":{"begin":1659,"end":1663},"obj":"Protein"},{"id":"T26176","span":{"begin":1668,"end":1673},"obj":"Protein"},{"id":"T26177","span":{"begin":1572,"end":1580},"obj":"Gene_expression"},{"id":"T26178","span":{"begin":1572,"end":1580},"obj":"Gene_expression"}],"relations":[{"id":"R19423","pred":"causeOf","subj":"T26162","obj":"T26164"},{"id":"R19424","pred":"themeOf","subj":"T26163","obj":"T26164"},{"id":"R19425","pred":"themeOf","subj":"T26171","obj":"T26177"},{"id":"R19426","pred":"themeOf","subj":"T26172","obj":"T26178"}],"text":"The Role of TGF-β in T Cell Differentiation\nAlthough TGF-β–reduced CD25, IL-4 expression, and CD25 expression (Figure 6B), IL-4 significantly inhibited TGF-β–mediated induction of FOXP3 in naive T cells driven toward FOXP3+ T cells, as shown by FACS analysis (Figure 6A). It is known that IL-4 is a potent growth factor and may therefore favor the proliferation of FOXP3– cells and thus decrease the relative percentage of FOXP3+ cells. However, analysis of cell division kinetics by CFSE-labeling demonstrated that IL-4 did not differentially promote cell growth of FOXP3+ over that of FOXP3–. In fact both populations showed similarly enhanced proliferation (Figure 6A). Furthermore the TGF-β–mediated induction of FOXP3 expression was not caused by overgrowth of a CD25–FOXP3+ minority, since the number of FOXP3+ cells was low/absent in the purified CD4+CD45RA+ T cells (between 0% and 1%), and the FOXP3+ cells were not confined to the highly divided cells. CD25 was down-regulated in TGF-β–treated cells compare to activated T cells, which was even more pronounced in cells cultured with TGF-β and IL-4.\nFigure 6 IL-4 Inhibits TGF-β–Mediated iTreg Commitment\nCFSE-labeled CD4+CD45RA+ cells were activated with plate-bound anti-CD3/CD28, TGF-β, and IL-4, as indicated. After 5 d, cells were analyzed by flow cytometry (A) and results of six independent experiments are shown in the bar graph below (B). Statistical significance (one-way Anova, Newman-Keuls) is indicated by asterisks (**p ≤ 0.01, ***p ≤ 0.001). (C) Kinetic analysis of intracellular GATA3 and FOXP3 staining is shown in panel C following exposure of CD4+CD45RA+ T cells to anti-CD3/28, IL-4 and TGF-β. Data are representative of three independent experiments. The addition of IL-4 to iTreg-driving conditions decreased the number of FOXP3+ cells (Figure 6B). In line with the previous findings, the IL-4–producing cells and the FOXP3 expressing cells are nonoverlapping populations. Since FOXP3 is known to act as a repressor of cytokine expression [20], we therefore analyzed GATA3 and FOXP3 expression. The expression kinetic of naive T cells exposed to IL-4 and TGF-β demonstrated that GATA3 and FOXP3 are initially found in separate populations (day 2), but transiently co-express both factors (days 4–8), before establishing separate populations at the end of the differentiation process (day 10; Figure 6C), suggesting that GATA3 inhibits the development of iTreg cells by repressing FOXP3.\nThese results showed that IL-4 acts in vitro as an inhibitor of FOXP3 expression, without interfering with TGF-β signaling, probably acting at the level of transcription factors, and possibly by a GATA3-dependent mechanism."}

bionlp-st-ge-2016-reference

bionlp-st-ge-2016-uniprot

test2

PMC:2222968 / 17545-20240 JSONTXT

Annnotations TAB JSON ListView MergeView

PMC:2222968 / 17545-20240 JSON TXT