IFNγ inhibits Th17 differentiation and function via Tbet-dependent and Tbet-independent mechanisms

•Tbet expression is not necessary for entry of CD4 T cells into the inflamed CNS.•CD4 T cell production of IL-17A is inhibited by Tbet in a cell-intrinsic manner.•Tbet expression is not critical for the induction of EAE.•IFNγ suppression of IL-17A is STAT1 dependent but Tbet independent.•However, IFNγ repression of RORγt expression is both STAT1 and Tbet dependent.

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.