RORγt represses IL-10 production in Th17 cells to maintain their pathogenicity in inducing intestinal inflammation

Mingming Sun, Chong He, Liang Chen, Wenjing Yang, Wei Wu, Feidi Chen, Anthony T. Cao, Suxia Yao, Sara Dann-Grice, T. G.Murali Dhar, Luisa Salter-Cid, Qihong Zhao, Zhanju Liu, Yingzi Cong

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)79-92
Number of pages14
JournalJournal of Immunology
Volume202
Issue number1
DOIs
StatePublished - Jan 1 2019

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Th17 Cells
Interleukin-10
Virulence
Inflammation
T-Lymphocytes
Colitis
Cell Differentiation
Retinoids
Cell Lineage
Cytokines

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

RORγt represses IL-10 production in Th17 cells to maintain their pathogenicity in inducing intestinal inflammation. / Sun, Mingming; He, Chong; Chen, Liang; Yang, Wenjing; Wu, Wei; Chen, Feidi; Cao, Anthony T.; Yao, Suxia; Dann-Grice, Sara; Dhar, T. G.Murali; Salter-Cid, Luisa; Zhao, Qihong; Liu, Zhanju; Cong, Yingzi.

In: Journal of Immunology, Vol. 202, No. 1, 01.01.2019, p. 79-92.

Research output: Contribution to journalArticle

Sun, M, He, C, Chen, L, Yang, W, Wu, W, Chen, F, Cao, AT, Yao, S, Dann-Grice, S, Dhar, TGM, Salter-Cid, L, Zhao, Q, Liu, Z & Cong, Y 2019, 'RORγt represses IL-10 production in Th17 cells to maintain their pathogenicity in inducing intestinal inflammation', Journal of Immunology, vol. 202, no. 1, pp. 79-92. https://doi.org/10.4049/jimmunol.1701697
Sun, Mingming ; He, Chong ; Chen, Liang ; Yang, Wenjing ; Wu, Wei ; Chen, Feidi ; Cao, Anthony T. ; Yao, Suxia ; Dann-Grice, Sara ; Dhar, T. G.Murali ; Salter-Cid, Luisa ; Zhao, Qihong ; Liu, Zhanju ; Cong, Yingzi. / RORγt represses IL-10 production in Th17 cells to maintain their pathogenicity in inducing intestinal inflammation. In: Journal of Immunology. 2019 ; Vol. 202, No. 1. pp. 79-92.
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