title: Deficiency of the G protein Gαq ameliorates experimental autoimmune encephalomyelitis with impaired DC-derived IL-6 production and Th17 differentiation.
abstract: Many G protein-coupled receptors (GPCRs) are reported to be involved in the pathogenesis of multiple sclerosis (MS), and ~40% of all identified GPCRs rely on the Gαq/11 G protein family to stimulate inositol lipid signaling. However, the function of Gα subunits in MS pathogenesis is still unknown. In this study, we attempted to determine the role of Gαq in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a well-known mouse model of MS. We discovered that compared with wild-type mice, Gαq-knockout mice exhibited less severe EAE symptoms, with lower clinical scores, reduced leukocyte infiltration and less extensive demyelination. Moreover, a significantly lower percentage of Th17 cells, one of the key players in MS pathogenesis, was observed in Gαq-knockout EAE mice. Studies in vitro demonstrated that deficiency of Gαq in CD4+T cells directly impaired Th17 differentiation. In addition, deficiency of Gαq significantly impaired DC-derived IL-6 production, thus inhibiting Th17 differentiation and the Gαq-PLCβ-PKC and Gαq-MAPKs signaling pathways involved in the reduced IL-6 production by DCs. In summary, our data highlighted the critical role of Gαq in regulating Th17 differentiation and MS pathogenesis.
authors.affiliation: Department of Central Laboratory, Shanghai Tenth People's Hospital of Tongji University, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Weiming
authors.initials: W
authors.lastname: Lai
authors.affiliation: Department of Central Laboratory, Shanghai Tenth People's Hospital of Tongji University, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Central Laboratory, Shanghai Tenth People's Hospital of Tongji University, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Central Laboratory, Shanghai Tenth People's Hospital of Tongji University, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Central Laboratory, Shanghai Tenth People's Hospital of Tongji University, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Chaoyan
authors.initials: C
authors.lastname: Qin
authors.affiliation: Department of Central Laboratory, Shanghai Tenth People's Hospital of Tongji University, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Cuixia
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Junling
authors.initials: J
authors.lastname: Liu
authors.affiliation: National Center for Drug Screening, CAS Key Laboratory of Receptor Research, Chinese Academy of Sciences, Shanghai Institute of Materia Medica, Shanghai 201203, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Central Laboratory, Shanghai Tenth People's Hospital of Tongji University, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.|Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Changsheng
authors.initials: C
authors.lastname: Du
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009103:Multiple Sclerosis / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D015850:Interleukin-6; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D043802:GTP-Binding Protein alpha Subunits, Gq-G11