Of a distant T-bet enhancer responsive to IL-12/Stat4 and IFNγ/Stat1 signals

被引：65

作者：

Yang, Yu

Ochando, Jordi C.

Bromberg, Jonathan S.

Ding, Yaozhong

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, Ctr Immunobiol, New York, NY 10029 USA

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

来源：

BLOOD | 2007年 / 110卷 / 07期

关键词：

IFN-GAMMA PRODUCTION; TRANSCRIPTION FACTOR; DNA-BINDING; LINEAGE COMMITMENT; INTERFERON-GAMMA; CELL-ACTIVATION; CUTTING EDGE; TH2; CELLS; EXPRESSION; DIFFERENTIATION;

D O I：

10.1182/blood-2006-11-058271

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

T-bet plays a critical role in controlling IFN gamma expression, Th1 polarization, and CD8 cytolytic development. Its regulation has been demonstrated to be mostly IFN gamma/Stat1 dependent while IL-12/Stat4 independent. Here we show that IL-12/Stat4 binds to a distant highly conserved STAT-responsive T-bet enhancer, and induces IFN gamma/Stat1-independent T-bet expression in CD8 T cells. Luciferase reporter assay showed that both Stat4 and Stat1 activate reporter gene expression from constructs containing a wild-type but not mutated T-bet enhancer. Studies in virus-infected mice demonstrated that the IL-12/Stat4/T-bet cascade operates in vivo and regulates IFN gamma in CD8 T cells. Together, we provide a novel mechanism for T-bet regulation, and suggest that IL-12/Stat4/T-bet play an important role in CD8 effector responses.

引用

页码：2494 / 2500

页数：7

共 39 条

[31] T-bet regulates the terminal maturation and homeostasis of NK and Vα14i NKT cells [J].