title: Suppression of Th17 cell differentiation by misshapen/NIK-related kinase MINK1.
abstract: T helper type 17 cells (Th17 cells) are major contributors to many autoimmune diseases. In this study, we demonstrate that the germinal center kinase family member MINK1 (misshapen/NIK-related kinase 1) negatively regulates Th17 cell differentiation. The suppressive effect of MINK1 on induction of Th17 cells is mediated by the inhibition of SMAD2 activation through direct phosphorylation of SMAD2 at the T324 residue. The importance of MINK1 to Th17 cell differentiation was strengthened in the animal model of experimental autoimmune encephalomyelitis (EAE). Moreover, we show that the reactive oxygen species (ROS) scavengerN-acetyl cysteine boosts Th17 cell differentiation in a MINK1-dependent manner and exacerbates the severity of EAE. Thus, we have not only established MINK1 as a critical regulator of Th17 cell differentiation, but also clarified that accumulation of ROS may limit the generation of Th17 cells. The contribution of MINK1 to ROS-regulated Th17 cell differentiation may suggest an important mechanism for the development of autoimmune diseases influenced by antioxidant dietary supplements.
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.|Program in Molecular and Cellular Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Guotong
authors.initials: G
authors.lastname: Fu
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.|Program in Molecular and Cellular Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.|Program in Molecular and Cellular Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Yuanjun
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.|Program in Molecular and Cellular Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Xuexiao
authors.initials: X
authors.lastname: Jin
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.|Program in Molecular and Cellular Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Xu
authors.affiliation: Life Sciences Institute, Zhejiang University, Hangzhou 310058, China.
authors.forename: Shunli
authors.initials: S
authors.lastname: Dong
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Jianli
authors.identifier: 0000-0001-8154-3063
authors.initials: J
authors.lastname: Wang
authors.affiliation: Program in Molecular and Cellular Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.|Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Yuehai
authors.initials: Y
authors.lastname: Ke
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Hu
authors.initials: H
authors.lastname: Hu
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.|Institute of Immunology and National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Xuetao
authors.initials: X
authors.lastname: Cao
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.|Program in Molecular and Cellular Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Di
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.|Department of Microbiology and Immunobiology, Division of Immunology, Harvard Medical School, Boston, MA 02115.
authors.forename: Harvey
authors.initials: H
authors.lastname: Cantor
authors.affiliation: Key Laboratory of Model Animals for Disease Study of the Ministry of Education, Model Animal Research Center, Nanjing University, Nanjing 210061, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China lu_linrong@zju.edu.cn.|Program in Molecular and Cellular Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.|Innovation Center for Cell Signaling Network, Zhejiang University School of Medicine, Hangzhou 310058, China.|Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Hangzhou 310058, China.|Dr. Li Dak Sum and Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Linrong
authors.identifier: 0000-0002-0171-4115
authors.initials: L
authors.lastname: Lu
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D051899:Smad2 Protein / Q000502:physiology; D058504:Th17 Cells / Q000502:physiology*
chemical_list: D017382:Reactive Oxygen Species; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; C533352:MINK7 protein, mouse; D017346:Protein Serine-Threonine Kinases