| First Author | Li C | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Pages | 14275 | PubMed ID | 28145433 |
| Mgi Jnum | J:244895 | Mgi Id | MGI:5913674 |
| Doi | 10.1038/ncomms14275 | Citation | Li C, et al. (2017) Dendritic cell MST1 inhibits Th17 differentiation. Nat Commun 8:14275 |
| abstractText | 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 alpha/beta 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. |
