Constitutive retinal CD200 expression regulates resident microglia and activation state of inflammatory cells during experimental autoimmune uveoretinitis.
Recent evidence supports the notion that tissue OX2 (CD200) constitutively provides down-regulatory signals to myeloid-lineage cells via CD200-receptor (CD200R). Thus, mice lacking CD200 (CD200(-/-)) show increased susceptibility to and accelerated onset of tissue-specific autoimmunity. In the retina there is extensive expression of CD200 on neurons and retinal vascular endothelium. We show here that retinal microglia in CD200(-/-) mice display normal morphology, but unlike microglia from wild-type CD200(+/+) mice are present in increased numbers and most significantly, express inducible nitric oxide synthase (NOS2), a macrophage activation marker. Onset and severity of uveitogenic peptide (1-20) of interphotoreceptor retinoid-binding protein-induced experimental autoimmune uveoretinitis is accelerated in CD200(-/-) mice and although tissue destruction appears no greater than seen in CD200(+/+) mice, there is continued increased ganglion and photoreceptor cell apoptosis. Myeloid cell infiltrate was increased in CD200(-/-) mice during experimental autoimmune uveoretinitis, although NOS2 expression was not heightened. The results indicate that the CD200:CD200R axis regulates retinal microglial activation. In CD200(-/-) mice the release of suppression of tonic macrophage activation, supported by increased NOS2 expression in the CD200(-/-) steady state accelerates disease onset but without any demonstration of increased target organ/tissue destruction.
Broderick
Cathryn
C
Department of Ophthalmology, University of Aberdeen, United Kingdom.
Hoek
Robert M
RM
Forrester
John V
JV
Liversidge
Janet
J
Sedgwick
Jonathon D
JD
Dick
Andrew D
AD
D000818:Animals; D015703:Antigens, CD; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017209:Apoptosis; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D039481:CD11b Antigen / Q000032:analysis; D002455:Cell Division; D002465:Cell Movement; D002478:Cells, Cultured; D018450:Disease Progression; D005136:Eye Proteins; D007962:Leukocytes / Q000737:chemistry / Q000276:immunology; D008262:Macrophage Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000166:cytology / Q000201:enzymology*; D022423:Myeloid Cells / Q000276:immunology; D019001:Nitric Oxide Synthase / Q000032:analysis; D052247:Nitric Oxide Synthase Type II; D010455:Peptides; D012160:Retina / Q000166:cytology* / Q000378:metabolism; D012173:Retinitis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D012177:Retinol-Binding Proteins / Q000737:chemistry; D014605:Uveitis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D000099214:Retinol-Binding Proteins, Interstitial
D015703:Antigens, CD; D000954:Antigens, Surface; D039481:CD11b Antigen; D005136:Eye Proteins; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D010455:Peptides; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial; C496317:Nos2 protein, mouse; C042739:antigens, CD200