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Nat Commun. 2017 Feb 1;8:14275. doi: 10.1038/ncomms14275.

Dendritic cell MST1 inhibits Th17 differentiation.

Li C1,2, Bi Y3, Li Y1,2, Yang H2, Yu Q1, Wang J1,2, Wang Y1,2, Su H1,2, Jia A1, Hu Y1, Han L1, Zhang J1, Li S1, Tao W4, Liu G1,2.

Author information

1
Key Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education, Institute of Cell Biology, College of Life Sciences, Beijing Normal University, Beijing 100875, China.
2
Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
3
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
4
State Key Laboratory of Genetic Engineering and Institute of Developmental Biology and Molecular Medicine, Collaborative Innovation Center of Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200433, China.

Abstract

Although the differentiation of CD4+T cells is widely studied, the mechanisms of antigen-presenting cell-dependent T-cell modulation are unclear. Here, we investigate the role of dendritic cell (DC)-dependent T-cell differentiation in autoimmune and antifungal inflammation and find that mammalian sterile 20-like kinase 1 (MST1) signalling from DCs negatively regulates IL-17 producing-CD4+T helper cell (Th17) differentiation. MST1 deficiency in DCs increases IL-17 production by CD4+T cells, whereas ectopic MST1 expression in DCs inhibits it. Notably, MST1-mediated DC-dependent Th17 differentiation regulates experimental autoimmune encephalomyelitis and antifungal immunity. Mechanistically, MST1-deficient DCs promote IL-6 secretion and regulate the activation of IL-6 receptor α/β and STAT3 in CD4+T cells in the course of inducing Th17 differentiation. Activation of the p38 MAPK signal is responsible for IL-6 production in MST1-deficient DCs. Thus, our results define the DC MST1-p38MAPK signalling pathway in directing Th17 differentiation.

PMID:
28145433
PMCID:
PMC5296641
DOI:
10.1038/ncomms14275
[Indexed for MEDLINE]
Free PMC Article

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