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Publication : Identification of a distant T-bet enhancer responsive to IL-12/Stat4 and IFNgamma/Stat1 signals.

First Author  Yang Y Year  2007
Journal  Blood Volume  110
Issue  7 Pages  2494-500
PubMed ID  17575072 Mgi Jnum  J:147019
Mgi Id  MGI:3839090 Doi  10.1182/blood-2006-11-058271
Citation  Yang Y, et al. (2007) Identification of a distant T-bet enhancer responsive to IL-12/Stat4 and IFNgamma/Stat1 signals. Blood 110(7):2494-500
abstractText  T-bet plays a critical role in controlling IFNgamma expression, Th1 polarization, and CD8 cytolytic development. Its regulation has been demonstrated to be mostly IFNgamma/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 IFNgamma/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 IFNgamma 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.
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