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Dendritic cell MST1 inhibits Th17 differentiation

Li, C;Bi, Y;Li, Y;Yang, H;Yu, Q;Wang, J;Wang, Y;Su, H;Jia, A;Hu, Y;Han, L;Zhang, J;Li, S;Tao, W;Liu, G;

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 / 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.