Sox5 and c-Maf cooperatively induce Th17 cell differentiation via ROR?t induction as downstream targets of Stat3.

ABSTRACT: Stat3 signaling is essential for the induction of ROR?t and subsequent Th17 cell differentiation. However, the downstream targets of Stat3 for ROR?t expression remain largely unknown. We show here that a novel isoform of Sox5, named Sox5t, is induced in Th17 cells in a Stat3-dependent manner. In vivo, T cell-specific Sox5-deficient mice exhibit impaired Th17 cell differentiation and are resistant to experimental autoimmune encephalomyelitis and delayed-type hypersensitivity. Retrovirus-mediated induction of Sox5 together with c-Maf induces Th17 cell differentiation even in Stat3-deficient CD4(+) T cells but not in ROR?t-deficient CD4(+) T cells, indicating that Sox5 and c-Maf induce Th17 cell differentiation as downstream effectors of Stat3 and as upstream inducers of ROR?t. Moreover, Sox5 physically associates with c-Maf via the HMG domain of Sox5 and DNA-binding domain of c-Maf, and Sox5 together with c-Maf directly activates the promoter of ROR?t in CD4(+) T cells. Collectively, our results suggest that Sox5 and c-Maf cooperatively induce Th17 cell differentiation via the induction of ROR?t as downstream targets of Stat3.

SUBMITTER: Tanaka S 

PROVIDER: S-EPMC4144730 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature