T-bet and Eomesodermin Play Critical Roles in Directing T Cell Differentiation to Th1 versus Th17

被引：97

作者：

Yang, Yu ^{[1
,4
]}

Xu, Jiangnan ^{[1
]}

Niu, Yanyan ^{[1
]}

Bromberg, Jonathan S. ^{[1
,2
,3
,4
]}

Ding, Yaozhong ^{[1
,2
,3
,4
]}

机构：

[1] Mt Sinai Sch Med, Dept Gene & Cell Med, New York, NY 10029 USA

[2] Mt Sinai Sch Med, Dept Surg, New York, NY 10029 USA

[3] Mt Sinai Sch Med, Inst Immunol, New York, NY 10029 USA

[4] Mt Sinai Sch Med, Recanati Miller Transplantat Inst, New York, NY 10029 USA

来源：

JOURNAL OF IMMUNOLOGY | 2008年 / 181卷 / 12期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.4049/jimmunol.181.12.8700

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Th1 and Th17 cells are crucial in immune regulation and autoimmune disease development. By adding Stat6 deficiency to T-bet deficiency, and thus negating effects from elevated levels of IL-4/Stat6/GATA3 Th2 signals in T-bet-deficient cells, we investigated the signals important for Th1 and Th17 cell differentiation and their role in colitis development. The data reveal that Eomesodermin compensates T-bet deficiency for IFN-gamma and Th1 development. However, without T-bet, IFN-gamma production and Th1 differentiation are susceptible to inhibition by IL-6 and TGF beta. As a result, Th17 development is strongly favored, the threshold for TGF beta requirement is lowered, and IL-6 drives Th17 differentiation, elucidating a critical role for T-bet in directing T cell differentiation to Th1 vs Th17. In contrast to IL-6 plus TGF beta-driven Th17, IIL-6-driven Th17 cells do not express IL-10 and they induce a more intense colitis. Naive CD4 T cells deficient in Stat6 and T-bet also induce a Th17-dominant colitis development in vivo. Our data provide new insights into the choice between Th1 and Th17 development and their roles in autoimmunity. The Journal of Immunology, 2008, 181: 8700-8710.

引用

页码：8700 / 8710

页数：11

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