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 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.
Izikson
L
L
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Klein
R S
RS
Charo
I F
IF
Weiner
H L
HL
Luster
A D
AD
D000818:Animals; D002490:Central Nervous System / Q000276:immunology / Q000473:pathology; D018932:Chemokine CCL2 / Q000096:biosynthesis; D018946:Chemokine CCL5 / Q000096:biosynthesis; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000096:biosynthesis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000096:biosynthesis; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine