title: Adiponectin Suppresses T Helper 17 Cell Differentiation and Limits Autoimmune CNS Inflammation via the SIRT1/PPARγ/RORγt Pathway.
abstract: T helper 17 (Th17) cells are vital components of the adaptive immune system involved in the pathogenesis of most autoimmune and inflammatory syndromes, and adiponectin(ADN) is correlated with inflammatory diseases such as multiple sclerosis (MS) and type II diabetes. However, the regulatory effects of adiponectin on pathogenic Th17 cell and Th17-mediated autoimmune central nervous system (CNS) inflammation are not fully understood. In this study, we demonstrated that ADN could inhibit Th1 and Th17 but not Th2 cells differentiation in vitro. In the in vivo study, we demonstrated that ADN deficiency promoted CNS inflammation and demyelination and exacerbated experimental autoimmune encephalomyelitis (EAE), an animal model of human MS. Furthermore, ADN deficiency increased the Th1 and Th17 cell cytokines of both the peripheral immune system and CNS in mice suffering from EAE. It is worth mentioning that ADN deficiency predominantly promoted the antigen-specific Th17 cells response in autoimmune encephalomyelitis. In addition, in vitro and in vivo, ADN upregulated sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor γ (PPARγ) and inhibited retinoid-related orphan receptor-γt (RORγt); the key transcription factor during Th17 cell differentiation. These results systematically uncovered the role and mechanism of adiponectin on pathogenic Th17 cells and suggested that adiponectin could inhibit Th17 cell-mediated autoimmune CNS inflammation.
authors: Department of Immunology, Research Center of Basic Medical Sciences, Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China, Tianjin Medical University, Tianjin, 300070, China.|Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, 300070, China.
authors: Kai
authors: K
authors: Zhang
authors: Department of Family Medicine and Primary Care, Department of Medicine, The University of Hong Kong, Hong Kong, China.
authors: Yawei
authors: Y
authors: Guo
authors: Department of Immunology, Research Center of Basic Medical Sciences, Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China, Tianjin Medical University, Tianjin, 300070, China.
authors: Zhenzhen
authors: Z
authors: Ge
authors: Department of Immunology, Research Center of Basic Medical Sciences, Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China, Tianjin Medical University, Tianjin, 300070, China.
authors: Zhihui
authors: Z
authors: Zhang
authors: Department of Immunology, Research Center of Basic Medical Sciences, Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China, Tianjin Medical University, Tianjin, 300070, China.
authors: Yurong
authors: Y
authors: Da
authors: Department of Immunology, Research Center of Basic Medical Sciences, Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China, Tianjin Medical University, Tianjin, 300070, China.
authors: Wen
authors: W
authors: Li
authors: Department of Immunology, Research Center of Basic Medical Sciences, Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China, Tianjin Medical University, Tianjin, 300070, China.
authors: Zimu
authors: Z
authors: Zhang
authors: Department of Immunology, Research Center of Basic Medical Sciences, Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China, Tianjin Medical University, Tianjin, 300070, China.
authors: Zhenyi
authors: Z
authors: Xue
authors: Department of Immunology, Research Center of Basic Medical Sciences, Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China, Tianjin Medical University, Tianjin, 300070, China.
authors: Yan
authors: Y
authors: Li
authors: Department of Immunology, Research Center of Basic Medical Sciences, Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China, Tianjin Medical University, Tianjin, 300070, China.
authors: Yinghui
authors: Y
authors: Ren
authors: Department of Immunology, Research Center of Basic Medical Sciences, Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China, Tianjin Medical University, Tianjin, 300070, China.
authors: Long
authors: L
authors: Jia
authors: State Key laboratory of Pharmaceutical Biotechnology, and Department of Medicine, The University of Hong Kong, Hong Kong, China.
authors: Koon-Ho
authors: KH
authors: Chan
authors: Department of Immunology, Research Center of Basic Medical Sciences, Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China, Tianjin Medical University, Tianjin, 300070, China.
authors: Fengrui
authors: F
authors: Yang
authors: Tianjin Animal Science and Veterinary Research Institute, Tianjin, 300381, China.
authors: Jun
authors: J
authors: Yan
authors: Department of Immunology, Research Center of Basic Medical Sciences, Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China, Tianjin Medical University, Tianjin, 300070, China.
authors: Zhi
authors: Z
authors: Yao
authors: State Key laboratory of Pharmaceutical Biotechnology, and Department of Medicine, The University of Hong Kong, Hong Kong, China.
authors: Aimin
authors: A
authors: Xu
authors: Department of Immunology, Research Center of Basic Medical Sciences, Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China, Tianjin Medical University, Tianjin, 300070, China. rongxinz@yahoo.com.|Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, 300070, China. rongxinz@yahoo.com.
authors: Rongxin
authors: R
authors: Zhang
mesh_terms: D052242:Adiponectin / Q000494:pharmacology*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002490:Central Nervous System / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D005260:Female; D008810:Mice, Inbred C57BL; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology*
chemical_list: D052242:Adiponectin; D016207:Cytokines; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D047495:PPAR gamma; D056564:Sirtuin 1
keywords: Adiponectin; Experimental autoimmune encephalomyelitis; PPARγ; RORγt; SIRT1; Th17 cell