Identification of a distant T-bet enhancer responsive to IL-12/Stat4 and IFNγ/Stat1 signals-Reference-Cited by-同舟云学术

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

Published:2007-10-01 Issue:7 Volume:110 Page:2494-2500
ISSN:0006-4971
Container-title:Blood
language:en
Short-container-title:

Author:

Yang Yu¹,Ochando Jordi C.¹,Bromberg Jonathan S.¹²³⁴,Ding Yaozhong¹²³⁴

Affiliation:

1. Departments ofGene and Cell Medicine, and

2. Surgery,

3. Center for Immunobiology, and

4. The Recanati/Miller Transplantation Institute, Mount Sinai School of Medicine, New York, NY

Abstract

T-bet plays a critical role in controlling IFNγ expression, Th1 polarization, and CD8 cytolytic development. Its regulation has been demonstrated to be mostly IFNγ/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 IFNγ/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 IFNγ 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.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

Link

http://ashpublications.org/blood/article-pdf/110/7/2494/483670/zh801907002494.pdf

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