title: CXCR7 suppression modulates microglial chemotaxis to ameliorate experimentally-induced autoimmune encephalomyelitis.
abstract: Multiple sclerosis (MS) is the prototypical inﬂammatory demyelinating disease of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE), widely used as an animal model of MS, classically manifests as an ascending paralysis that is characterized by extensive infiltration of the CNS by inflammatory cells. Although several studies uncover the significant role of microglia in the development of EAE, the cellular mechanisms of microglia that govern EAE pathogenesis remain unknown. In the current study, we report that CXCR7 expression is dynamic regulated in activated microglia during CNS autoimmunity and positively correlates with the clinical severity of EAE. In addition, microglial chemotaxis is mediated by CXCR7 during CNS autoimmunity, signaling through extracellular signal-regulated kinase (ERK)1/2 activation, whereas p38 mitogen-activated protein kinase (MAPK) and (c-Jun N-terminal kinase) JNK are not involved. Most importantly, CXCR7 neutralizing treatment ameliorates the clinical severity of EAE along with ERK1/2 phosphorylation reduction. Collectively, our data demonstrate that CXCR7 suppression modulates microglial chemotaxis to ameliorate EAE.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, China.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Bao
authors.affiliation: Department of Mental Health, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, China.
authors.forename: Jinying
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Luo
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, China. Electronic address: zhou_sj@tom.com.
authors.forename: Saijun
authors.initials: S
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002633:Chemotaxis / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D020935:MAP Kinase Signaling System / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000276:immunology*; D009103:Multiple Sclerosis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D054387:Receptors, CXCR / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; C501897:Cmkor1 protein, mouse; D007166:Immunosuppressive Agents; D054387:Receptors, CXCR
keywords: CXCR7; Chemotaxis; Experimentally-induced autoimmune encephalomyelitis (EAE); Extracellular signal-regulated kinase (ERK); Microglia