| First Author | Tanaka S | Year | 2014 |
| Journal | J Exp Med | Volume | 211 |
| Issue | 9 | Pages | 1857-74 |
| PubMed ID | 25073789 | Mgi Jnum | J:218117 |
| Mgi Id | MGI:5616689 | Doi | 10.1084/jem.20130791 |
| Citation | Tanaka S, et al. (2014) Sox5 and c-Maf cooperatively induce Th17 cell differentiation via RORgammat induction as downstream targets of Stat3. J Exp Med 211(9):1857-74 |
| abstractText | Stat3 signaling is essential for the induction of RORgammat and subsequent Th17 cell differentiation. However, the downstream targets of Stat3 for RORgammat 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 RORgammat-deficient CD4(+) T cells, indicating that Sox5 and c-Maf induce Th17 cell differentiation as downstream effectors of Stat3 and as upstream inducers of RORgammat. 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 RORgammat in CD4(+) T cells. Collectively, our results suggest that Sox5 and c-Maf cooperatively induce Th17 cell differentiation via the induction of RORgammat as downstream targets of Stat3. |
