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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

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

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.[1]

References

  1. Identification of a distant T-bet enhancer responsive to IL-12/Stat4 and IFNgamma/Stat1 signals. Yang, Y., Ochando, J.C., Bromberg, J.S., Ding, Y. Blood (2007) [Pubmed]
 
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