title: IFN-β inhibits T cells accumulation in the central nervous system by reducing the expression and activity of chemokines in experimental autoimmune encephalomyelitis.
abstract: Multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), are chronic neuroinflammatory autoimmune diseases characterized by axonal loss, demyelination and neurodegeneration of the central nervous system (CNS). Overactivation of CD4(+)T cells, especially the Th1 and Th17 subsets, is thought to play a causal role in this disease. In this study, we investigated the immunomodulatory effects of IFN-β treatment in EAE. IFN-β significantly inhibits disease severity, and decreases levels of CCR2, CCR4, CCR5, CCR6 and CXCR3 in the CNS. This was associated with fewer Th1/Th17 cells expressing these chemokine receptors. Furthermore, levels of their corresponding ligands CCL2, CCL3, CCL4, CCL5, CCL20, CCL22 and CXCL10 were also reduced, coinciding with reduced CNS inflammation and demyelination. Chemokine expression significantly correlated with disease severity. Furthermore, we demonstrate that IFN-β reduces CCL2/CCL5 induced-T cell migration by inhibiting p38-MAPK and ERK1/2 activation. Our results reveal that IFN-β reduces the expression of chemokines and chemokine receptors expressed by encephalitogenic Th1/Th17 cells, thereby decreasing their migration into the CNS.
authors.affiliation: Department of Immunology and Microbiology, Shanghai JiaoTong University School of Medicine, Shanghai Institute of Immunology, PR China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Cheng
authors.affiliation: Department of Immunology and Microbiology, Shanghai JiaoTong University School of Medicine, Shanghai Institute of Immunology, PR China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of Immunology and Microbiology, Shanghai JiaoTong University School of Medicine, Shanghai Institute of Immunology, PR China.
authors.forename: Yebin
authors.initials: Y
authors.lastname: Xi
authors.affiliation: Department of Immunology and Microbiology, Shanghai JiaoTong University School of Medicine, Shanghai Institute of Immunology, PR China.
authors.forename: Chengzhen
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Immunology and Microbiology, Shanghai JiaoTong University School of Medicine, Shanghai Institute of Immunology, PR China.
authors.forename: Yunzhi
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Immunology and Microbiology, Shanghai JiaoTong University School of Medicine, Shanghai Institute of Immunology, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Immunology and Microbiology, Shanghai JiaoTong University School of Medicine, Shanghai Institute of Immunology, PR China. Electronic address: niuxiaoyin@163.com.
authors.forename: Xiaoyin
authors.initials: X
authors.lastname: Niu
authors.affiliation: Department of Immunology and Microbiology, Shanghai JiaoTong University School of Medicine, Shanghai Institute of Immunology, PR China. Electronic address: zjwang@sjtu.edu.cn.
authors.forename: Zhaojun
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Immunology and Microbiology, Shanghai JiaoTong University School of Medicine, Shanghai Institute of Immunology, PR China. Electronic address: guangjie_chen@163.com.
authors.forename: Guangjie
authors.initials: G
authors.lastname: Chen
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects / Q000276:immunology* / Q000473:pathology*; D018925:Chemokines / Q000378:metabolism*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016899:Interferon-beta / Q000494:pharmacology / Q000627:therapeutic use*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008810:Mice, Inbred C57BL; D063308:Myelin-Oligodendrocyte Glycoprotein; D019707:Receptors, Chemokine / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D018925:Chemokines; D063308:Myelin-Oligodendrocyte Glycoprotein; D019707:Receptors, Chemokine; D016899:Interferon-beta; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Chemokine; Chemokine receptors; EAE; IFN-β; Th1; Th17