Resistance to Experimental Autoimmune Encephalomyelitis in Mice Lacking the Cc Chemokine Receptor (Ccr2)

TLDR

Monocyte recruitment to the CNS is essential for inflammatory lesion formation in EAE, with MCP‑1 driving this process. The study tests whether loss of CCR2, the MCP‑1 receptor, protects mice from MOGp35‑55–induced EAE. CCR2‑deficient mice show no CNS inflammatory infiltrates, no chemokine up‑regulation, and reduced T‑cell proliferation and IFN‑γ production, demonstrating CCR2’s essential, nonredundant role in EAE pathogenesis.

Abstract

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.