Resistance to experimental autoimmune encephalomyelitis in mice lacking the CC chemokine receptor (CCR2)

L Izikson, RS Klein, IF Charo, HL Weiner… - The Journal of …, 2000 - rupress.org
L Izikson, RS Klein, IF Charo, HL Weiner, AD Luster
The Journal of experimental medicine, 2000rupress.org
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 …
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-γ 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.
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