title: Dendritic cell MST1 inhibits Th17 differentiation.
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.
authors.affiliation: 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.|Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Li
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Yujing
authors.initials: Y
authors.lastname: Bi
authors.affiliation: 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.|Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yu
authors.affiliation: 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.|Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: 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.|Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 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.|Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Huilin
authors.initials: H
authors.lastname: Su
authors.affiliation: 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.
authors.forename: Anna
authors.initials: A
authors.lastname: Jia
authors.affiliation: 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.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.affiliation: 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.
authors.forename: Linian
authors.initials: L
authors.lastname: Han
authors.affiliation: 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.
authors.forename: Jiangyuan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Simin
authors.initials: S
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Wufan
authors.initials: W
authors.lastname: Tao
authors.affiliation: 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.|Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Guangwei
authors.initials: G
authors.lastname: Liu
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology / Q000378:metabolism; D000099317:Hippo Kinases
chemical_list: D020381:Interleukin-17; D015850:Interleukin-6; D017346:Protein Serine-Threonine Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C490660:Stk4 protein, mouse; D000099317:Hippo Kinases