Dendritic cell MST1 inhibits Th17 differentiation.

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.

Citation

Chunxiao Li, Yujing Bi, Yan Li, Hui Yang, Qing Yu, Jian Wang, Yu Wang, Huilin Su, Anna Jia, Ying Hu, Linian Han, Jiangyuan Zhang, Simin Li, Wufan Tao, Guangwei Liu. Dendritic cell MST1 inhibits Th17 differentiation. Nature communications. 2017 Feb 01;8:14275

PMID: 28145433

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