Chemokine-like receptor-1 expression by central nervous system-infiltrating leukocytes and involvement in a model of autoimmune demyelinating disease.
We examined the involvement of chemokine-like receptor-1 (CMKLR1) in experimental autoimmune encephalomyelitis (EAE), a model of human multiple sclerosis. Upon EAE induction by active immunization with myelin oligodendrocyte glycoprotein amino acids 35-55 (MOG(35-55)), microglial cells and CNS-infiltrating myeloid dendritic cells expressed CMKLR1, as determined by flow cytometric analysis. In addition, chemerin, a natural ligand for CMKLR1, was up-regulated in the CNS of mice with EAE. We found that CMKLR1-deficient (CMKLR1 knockout (KO)) mice develop less severe clinical and histologic disease than their wild-type (WT) counterparts. CMKLR1 KO lymphocytes proliferate and produce proinflammatory cytokines in vitro, yet MOG(35-55)-reactive CMKLR1 KO lymphocytes are deficient in their ability to induce EAE by adoptive transfer to WT or CMKLR1 KO recipients. Moreover, CMKLR1 KO recipients fail to fully support EAE induction by transferred MOG-reactive WT lymphocytes. The results imply involvement of CMKLR1 in both the induction and effector phases of disease. We conclude that CMKLR1 participates in the inflammatory mechanisms of EAE and represents a potential therapeutic target in multiple sclerosis.
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA. kareem.graham@stanford.edu
Kareem L
KL
Graham
Brian A
BA
Zabel
Sanam
S
Loghavi
Luis A
LA
Zuniga
Peggy P
PP
Ho
Raymond A
RA
Sobel
Eugene C
EC
Butcher
D019264:Adoptive Transfer; D000818:Animals; D002490:Central Nervous System / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018925:Chemokines; D002630:Chemotactic Factors / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006023:Glycoproteins / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000494:pharmacology; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
C486456:CMKLR1 protein, mouse; D018925:Chemokines; D002630:Chemotactic Factors; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D020381:Interleukin-17; D008070:Lipopolysaccharides; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled; D014409:Tumor Necrosis Factor-alpha; C523686:chemerin protein, mouse; C445081:myelin oligodendrocyte glycoprotein (35-55); D007371:Interferon-gamma