Resistance to experimental autoimmune encephalomyelitis in mice lacking the CC chemokine receptor (CCR)2

Monocyte recruitment to the central nervous system (CNS) is a necessary step in the development of pathologic inflammatory lesions in experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis. Monocyte chemoattractant protein (MCP)-1, a potent agonist for directed monocyt...

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Bibliographic Details
Published in:The Journal of experimental medicine 2000-10, Vol.192 (7), p.1075-1080
Main Authors: Izikson, L, Klein, R S, Charo, I F, Weiner, H L, Luster, A D
Format: Article
Language:English
Subjects:
Animals
Central Nervous System - immunology
Central Nervous System - pathology
Chemokine CCL2 - biosynthesis
Chemokine CCL5 - biosynthesis
Chemokine CXCL10
Chemokines, CXC - biosynthesis
Encephalomyelitis, Autoimmune, Experimental - immunology
Immunity, Innate - immunology
Mice
Mice, Inbred C57BL
Mice, Knockout
Myelin Proteins
Myelin-Associated Glycoprotein - immunology
Myelin-Oligodendrocyte Glycoprotein
Receptors, CCR2
Receptors, CCR5 - biosynthesis
Receptors, Chemokine - genetics
Receptors, Chemokine - immunology
T-Lymphocytes - immunology
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Summary:Monocyte recruitment to the central nervous system (CNS) is a necessary step in the development of pathologic inflammatory lesions in experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis. Monocyte chemoattractant protein (MCP)-1, a potent agonist for directed monocyte migration, has been implicated in the pathogenesis of EAE. Here we report that deficiency in CC chemokine receptor (CCR)2, the receptor for MCP-1, confers resistance to EAE induced with a peptide derived from myelin oligodendrocyte glycoprotein peptide 35-55 (MOGp35-55). CCR2(-/)- mice immunized with MOGp35-55 failed to develop mononuclear cell inflammatory infiltrates in the CNS and failed to increase CNS levels of the chemokines RANTES (regulated on activation, normal T cell expressed and secreted), MCP-1, and interferon (IFN)-inducible protein 10 (IP-10) as well the chemokine receptors CCR1, CCR2, and CCR5. Additionally, T cells from CCR2(-/)- immunized mice showed decreased antigen-induced proliferation and production of IFN-gamma compared with wild-type immunized controls, suggesting that CCR2 enhances the T helper cell type 1 immune response in EAE. These data indicate that CCR2 plays a necessary and nonredundant role in the pathogenesis of EAE.
ISSN:0022-1007
1892-1007
DOI:10.1084/jem.192.7.1075