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This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: jimmunol.0803435v1 183/10/6717    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Graham, K. L. Articles by Butcher, E. C. PubMed PubMed Citation Articles by Graham, K. L. Articles by Butcher, E. C.

Chemokine-Like Receptor-1 Expression by Central Nervous System-Infiltrating Leukocytes and Involvement in a Model of Autoimmune Demyelinating Disease¹

Kareem L. Graham,^2* Brian A. Zabel,^* Sanam Loghavi,^* Luis A. Zuniga,^* Peggy P. Ho, Raymond A. Sobel,^* and Eugene C. Butcher^2*

^*Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305 and Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304; and Department of Neurology, Stanford University School of Medicine, Stanford, CA 94305

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work is supported by National Institutes of Health Grants AI-59635, AI-47822, and GM-37734; Specialized Center of Research Grant HL-67674; and a Merit Award from the Veterans Administration to E.C.B. B.A.Z. is supported by National Institutes of Health Grant AI-079320 and SPARK awards from Stanford University. K.L.G. was supported by a United Negro College Fund Merck Postdoctoral Award and a postdoctoral fellowship from the National Multiple Sclerosis Society.

² Address correspondence to Dr. Graham, Veterans Affairs Palo Alto Health Care System, 3801 Miranda Avenue, Mail Code 154B, Palo Alto, CA 94304. E-mail address: kareem.graham{at}stanford.edu or Dr. Butcher, E-mail address: ebutcher{at}stanford.edu

³ Abbreviations used in this paper: EAE, experimental autoimmune encephalomyelitis; CMKLR1, chemokine-like receptor-1; DC, dendritic cell; KO, knockout; LN, lymph node; mDC, myeloid DC; MOG, myelin oligodendrocyte glycoprotein; MS, multiple sclerosis; pDC, plasmacytoid DC; p.i., postimmunization; PLC, peritoneal lavage cell; WT, wild type.

⁴ The online version of this article contains supplemental material.