CNS inflammation and neuronal degeneration is aggravated by impaired CD200-CD200R-mediated macrophage silencing.
Multiple sclerosis is a chronic disabling CNS disorder, characterized by autoimmune inflammatory demyelination and neurodegeneration. CD200, broadly expressed on neurons and endothelial cells, mediates inhibitory signals through its receptor, CD200R, on cells of myeloid origin. Antibody-mediated blockade of CD200R leads to an aggravated clinical course of rodent experimental autoimmune encephalomyelitis in vivo, accompanied by profoundly augmented cellular infiltrates consisting of T cells and activated iNOS(+) macrophages in inflammatory spinal cord lesions. In vitro blockade of CD200R on macrophages leads to enhanced IFN-gamma-induced release of IL6 and neuronal cell death in co-cultures with hippocampal neurons expressing CD200. CD200 and its receptor could also be detected on neurons and macrophages in human MS plaques. Therefore the CD200-CD200R pathway seems of critical relevance for macrophage-mediated damage in autoimmune inflammation of the CNS.
Meuth
Sven G
SG
University of Wuerzburg, Department of Neurology, Josef-Schneider-Strasse 11, 97080 Wuerzburg, Germany. meuth_s@klinik.uni-wuerzburg.de
Simon
Ole J
OJ
Grimm
Alexander
A
Melzer
Nico
N
Herrmann
Alexander M
AM
Spitzer
Philipp
P
Landgraf
Peter
P
Wiendl
Heinz
H
D000818:Animals; D000906:Antibodies / Q000494:pharmacology / Q000627:therapeutic use; D015703:Antigens, CD / Q000032:analysis / Q000502:physiology*; D000954:Antigens, Surface / Q000032:analysis / Q000502:physiology; D017209:Apoptosis; D002478:Cells, Cultured / Q000378:metabolism / Q000473:pathology; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism / Q000473:pathology*; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D015850:Interleukin-6 / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000737:chemistry / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000737:chemistry / Q000473:pathology; D064446:Orexin Receptors; D051381:Rats; D020318:Rats, Long-Evans; D011956:Receptors, Cell Surface / Q000032:analysis / Q000502:physiology; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology
D000906:Antibodies; D015703:Antigens, CD; D000954:Antigens, Surface; C492346:CD200 receptor, mouse; C477337:CD200R1 protein, human; C495490:Cd200 protein, rat; D016207:Cytokines; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D064446:Orexin Receptors; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D007371:Interferon-gamma; C042739:antigens, CD200