Negative Regulation of Autoimmune Demyelination by the Inhibitory Receptor CLM-1

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2009 Dec 30

PMID 20038601

Citations 36

Authors

Hongkang Xi

Kenneth J Katschke Jr

Karim Y Helmy

Paige A Wark

Noelyn Kljavin

Hilary Clark

Jeffrey Eastham-Anderson

Theresa Shek

Merone Roose-Girma

Nico Ghilardi

Menno van Lookeren Campagne

Affiliations

Soon will be listed here.

Abstract

Multiple sclerosis and its preclinical model, experimental autoimmune encephalomyelitis, are marked by perivascular inflammation and demyelination. Myeloid cells, derived from circulating progenitors, are a prominent component of the inflammatory infiltrate and are believed to directly contribute to demyelination and axonal damage. How the cytotoxic activity of these myeloid cells is regulated is poorly understood. We identify CMRF-35-like molecule-1 (CLM-1) as a negative regulator of autoimmune demyelination. CLM-1 is expressed on inflammatory myeloid cells present in demyelinating areas of the spinal cord after immunization of mice with MOG35-55 (myelin oligodendrocyte glycoprotein) peptide. Absence of CLM-1 resulted in significantly increased nitric oxide and proinflammatory cytokine production, along with increased demyelination and worsened clinical scores, whereas T cell responses in the periphery or in the spinal cord remained unaffected. This study thus identifies CLM-1 as a negative regulator of myeloid effector cells in autoimmune demyelination.

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