IFNγ inhibits Th17 differentiation and function via Tbet-dependent and Tbet-independent mechanisms
نویسندگان
چکیده
The transcription factor Tbet is critical for the differentiation of Th1 CD4 T cells and is associated with the induction of multiple autoimmune diseases, including experimental autoimmune encephalomyelitis (EAE). Herein, we demonstrate that Tbet suppresses IL-17A and Th17 differentiation both in vitro and in vivo in a cell-intrinsic manner, and that in fact, Tbet is not necessary for EAE induction. Moreover, we find that IFNγ inhibits the production of IL-17A and IL-17F in a STAT1-dependent, Tbet-independent manner. These findings illustrate multiple mechanisms utilized by developing Th1 cells to silence the Th17 program.
منابع مشابه
Autoreactive Tbet-positive CD4 T cells develop independent of classic Th1 cytokine signaling during experimental autoimmune encephalomyelitis.
Many autoimmune chronic inflammatory diseases, including multiple sclerosis, are associated with the presence of Th1 and Th17 effector CD4 T cells. Paradoxically, the principal Th1 cytokine IFN-γ does not appear necessary for disease, but the key Th1-associated transcription factor Tbet has been reported to be essential for disease development. This conundrum propelled us to investigate the reg...
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