| First Author | Sun M | Year | 2019 |
| Journal | J Immunol | Volume | 202 |
| Issue | 1 | Pages | 79-92 |
| PubMed ID | 30478092 | Mgi Jnum | J:329649 |
| Mgi Id | MGI:6754677 | Doi | 10.4049/jimmunol.1701697 |
| Citation | Sun M, et al. (2019) RORgammat Represses IL-10 Production in Th17 Cells To Maintain Their Pathogenicity in Inducing Intestinal Inflammation. J Immunol 202(1):79-92 |
| abstractText | The role of retinoid-related orphan receptor gamma t (RORgammat) in Th17 cell differentiation has been well established; however, how it regulates other T cell lineages is still not clearly understood. In this study, we report that in mice, while promoting Th17 cell differentiation, RORgammat inhibited IL-10 production by T cells, thereby preserving the pathogenicity of Th17 cells. Treatment with RORgammat-specific inhibitor suppressed Th17 cell signature cytokines, but promoted IL-10 production. RORgammat inhibitor-treated Th17 cells induce less severe colitis compared with control Th17 cells. Mechanistically, the RORgammat inhibitor induced T cell expression of Blimp-1 (encoded by Prdm1). Prdm1(-/-) T cells produced significantly fewer IL-10 when treated with RORgammat inhibitor compared with wild-type T cells. Furthermore, RORgammat inhibitor-treated Prdm1(-/-) Th17 cells induce more severe colitis compared with RORgammat inhibitor-treated wild-type Th17 cells. Collectively, our studies reveal a novel mechanism by which RORgammat drives and maintains pathogenic Th17 cell development by inhibiting IL-10 production. |
