Negative regulation of autoimmune demyelination by the inhibitory receptor CLM-1.
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.
Xi
Hongkang
H
Department of Immunology, Genentech Inc., South San Francisco, CA 94080, USA.
Katschke
Kenneth J
KJ
Helmy
Karim Y
KY
Wark
Paige A
PA
Kljavin
Noelyn
N
Clark
Hilary
H
Eastham-Anderson
Jeffrey
J
Shek
Theresa
T
Roose-Girma
Merone
M
Ghilardi
Nico
N
van Lookeren Campagne
Menno
M
D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006023:Glycoproteins / Q000009:adverse effects / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009103:Multiple Sclerosis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D063308:Myelin-Oligodendrocyte Glycoprotein; D022423:Myeloid Cells / Q000276:immunology* / Q000473:pathology; D009569:Nitric Oxide / Q000235:genetics / Q000276:immunology; D010446:Peptide Fragments / Q000009:adverse effects / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology*
C482560:CLM-1 protein, mouse; D016207:Cytokines; D006023:Glycoproteins; D018836:Inflammation Mediators; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D011971:Receptors, Immunologic; C445081:myelin oligodendrocyte glycoprotein (35-55); D009569:Nitric Oxide