Dendritic Cell MST1 Inhibits Th17 Differentiation

Overview

Journal Nat Commun

Specialty Biology

Date 2017 Feb 2

PMID 28145433

Citations 40

Authors

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

Affiliations

Soon will be listed here.

Abstract

Although the differentiation of CD4T 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-CD4T helper cell (Th17) differentiation. MST1 deficiency in DCs increases IL-17 production by CD4T 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 CD4T 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.

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