| Literature DB >> 30478092 |
Mingming Sun1,2, Chong He1,2, Liang Chen1,2, Wenjing Yang1,2, Wei Wu1,2, Feidi Chen3, Anthony T Cao1, Suxia Yao1, Sara M Dann4, T G Murali Dhar5, Luisa Salter-Cid5, Qihong Zhao5, Zhanju Liu6, Yingzi Cong7,3.
Abstract
The role of retinoid-related orphan receptor γ t (RORγt) 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, RORγt inhibited IL-10 production by T cells, thereby preserving the pathogenicity of Th17 cells. Treatment with RORγt-specific inhibitor suppressed Th17 cell signature cytokines, but promoted IL-10 production. RORγt inhibitor-treated Th17 cells induce less severe colitis compared with control Th17 cells. Mechanistically, the RORγt inhibitor induced T cell expression of Blimp-1 (encoded by Prdm1). Prdm1-/- T cells produced significantly fewer IL-10 when treated with RORγt inhibitor compared with wild-type T cells. Furthermore, RORγt inhibitor-treated Prdm1-/- Th17 cells induce more severe colitis compared with RORγt inhibitor-treated wild-type Th17 cells. Collectively, our studies reveal a novel mechanism by which RORγt drives and maintains pathogenic Th17 cell development by inhibiting IL-10 production.Entities:
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Year: 2018 PMID： 30478092 PMCID： PMC6310078 DOI： 10.4049/jimmunol.1701697
Source DB: PubMed Journal: J Immunol ISSN： 0022-1767 Impact factor: 5.422