title: Astrocyte CCL2 sustains immune cell infiltration in chronic experimental autoimmune encephalomyelitis.
abstract: Chemokine (C-C motif) ligand 2 (CCL2), initially identified as monocyte chemoattractant protein-1 (MCP-1), recruits immune cells to the central nervous system (CNS) during autoimmune inflammation. CCL2 can be expressed by multiple cell types, but which cells are responsible for CCL2 function during acute and chronic phases of autoimmune disease is not known. We determined the role of CCL2 in astrocytes in vivo during experimental autoimmune encephalomyelitis (EAE) by using Cre-loxP gene deletion. Mice with a conditional gene deletion of CCL2 from astrocytes had less severe EAE late in disease while having a similar incidence and severity of disease at onset as compared to wild type (WT) control littermates. EAE mice devoid of CCL2 in astrocytes had less macrophage and T cell inflammation in the white matter of the spinal cord and less diffuse activation of astrocytes and microglia in both white and gray matter as well as less axonal loss and demyelination, compared to WT littermates. These findings demonstrate that CCL2 in astrocytes plays an important role in the continued recruitment of immune cells and activation of glial cells in the CNS during chronic EAE, thereby suggesting a novel cell specific target for neuroprotective treatments of chronic neuroinflammatory diseases.
authors.affiliation: Molecular Cellular and Integrative Physiology Interdepartmental Ph.D. Program, University of California, Los Angeles; Multiple Sclerosis Program, Department of Neurology, University of California, Los Angeles.
authors.forename: Roy Y
authors.initials: RY
authors.lastname: Kim
authors.affiliation: Multiple Sclerosis Program, Department of Neurology, University of California, Los Angeles.
authors.forename: Alexandria S
authors.initials: AS
authors.lastname: Hoffman
authors.affiliation: Multiple Sclerosis Program, Department of Neurology, University of California, Los Angeles.
authors.forename: Noriko
authors.initials: N
authors.lastname: Itoh
authors.affiliation: Department of Neurobiology, University of California, Los Angeles.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ao
authors.affiliation: Multiple Sclerosis Program, Department of Neurology, University of California, Los Angeles.
authors.forename: Rory
authors.initials: R
authors.lastname: Spence
authors.affiliation: Department of Neurobiology, University of California, Los Angeles.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Sofroniew
authors.affiliation: Multiple Sclerosis Program, Department of Neurology, University of California, Los Angeles. Electronic address: rvoskuhl@ucla.edu.
authors.forename: Rhonda R
authors.initials: RR
authors.lastname: Voskuhl
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000276:immunology*; D018932:Chemokine CCL2 / Q000235:genetics / Q000276:immunology*; D002908:Chronic Disease; D003711:Demyelinating Diseases / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology*; D005260:Female; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000276:immunology; D009186:Myelin Sheath / Q000276:immunology; D013116:Spinal Cord / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2
keywords: Astrocytes; CCL2; EAE; Macrophage; Microglia; Multiple Sclerosis; Neuroprotection; T lymphocyte