IRF4 is essential for IL-21-mediated induction, amplification, and stabilization of the Th17 phenotype.

ABSTRACT: Differentiation of murine T-helper (Th) 17 cells is induced by antigenic stimulation and the sequential action of the cytokines IL-6, IL-21, and IL-23, along with TGFbeta. Current dogma proposes that IL-6 induces IL-21, which, in a STAT3-dependent manner, amplifies its own transcription, contributes to IL-17 production, and, moreover, promotes the expression of the IL-23 receptor. This, in turn, prepares cells for IL-23-mediated stabilization of the Th17 phenotype. Here we demonstrate that these effects of IL-21 on Th17 differentiation are completely dependent on IFN regulatory factor 4 (IRF4). After culturing in the presence of IL-21 plus TGFbeta, IRF4-deficient (Irf4(-/-)) Th cells showed a profound intrinsic defect in IL-17 production and in the autocrine IL-21 loop. Likewise, the level

SUBMITTER: Huber M 

PROVIDER: S-EPMC2634912 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature