Expression of chemokine-like receptor-1 (CMKLR1) and chemerin within the central nervous system: implications for regulation of experimental autoimmune encephalomyelitis

Background: Chemoattractant receptors, adhesion molecules, and their ligands have been implicated in recruitment of inflammatory cells to the central nervous system (CNS) during multiple sclerosis (MS). Chemokine-like receptor-1 (CMKLR1; also known as ChemR23 or Dez) is a G protein-coupled receptor that shares phylogenetic homology with a subfamily of chemoattractant receptors, including C5a-R and C3a-R. CMKLR1 is primarily expressed by monocytes, macrophages, and plasmacytoid dendritic cells. We have previously shown that CMKLR1-deficient mice are resistant to progressive experimental autoimmune encephalomyelitis (EAE), a model for human MS. It also has been shown that mRNA for chemerin, a natural ligand for CMKLR1 and a proteolytically regulated chemoattractant, is expressed at relatively low levels in the CNS. Objective: We sought to determine sources of chemerin within the CNS, as well as to identify CMKLR1-expressing cells in the CNS of mice with clinical EAE. Methods: We used a novel anti-CMKLR1 monoclonal antibody to examine CMKLR1 expression on primary mouse CNS mononuclear cells and a microglial cell line. We developed an enzyme-linked immunosorbent assay (ELISA) to measure chemerin levels in vitro. Results: CMKLR1 and chemerin are expressed in the spinal cord of mice with EAE. Flow cytometric analysis indicates that a subset of CNS-infiltrating macrophages express CMKLR1 during acute EAE, while mouse microglia constitutively express CMKLR1. Mouse brain extract contains detectable levels of chemerin protein, and microglia produce chemerin in response to stimulation with tumor growth factor beta in vitro. Conclusions: These data implicate CNS-resident microglia as a potential source of active chemerin, which may serve to recruit CMKLR1-expressing cells to inflammatory lesions during EAE.