Monoclonal antibody-mediated CD200 receptor signaling suppresses macrophage activation and tissue damage in experimental autoimmune uveoretinitis

DA Copland, CJ Calder, BJE Raveney, LB Nicholson, J Phillips, H Cherwinski, M Jenmalm, JD Sedgwick, AD Dick

Research output: Contribution to journalArticle (Academic Journal)

93 Citations (Scopus)

Abstract

Macrophage responses are regulated by multiple secreted factors as well as by cell surface receptors, including the inhibitory signals resulting from ligation of myeloid CD200 receptors (CD200R) by the widely distributed CD200. In the absence of CD200, animals display increased susceptibility to autoimmunity and earlier onset aggressive autoimmune disease. In these current experiments, an agonist monoclonal rat anti-mouse CD200R (DX109) antibody delivered a negative signal to bone marrow-derived macrophages, which suppressed interferon (IFN){gamma}-mediated nitric oxide (NO) and interleukin-6 production. Experimental autoimmune uveoretinitis (EAU) was used as a model of organ-specific autoimmunity in the eye, a tissue with extensive neuronal and endothelial CD200 expression. In mice lacking CD200 (CD200–/–), increased numbers of retina-infiltrating macrophages displaying heightened NO responses were observed during EAU. In addition, we aimed to suppress disease by maintaining tonic suppression of macrophage activation via CD200R. Systemically administered DX109 monoclonal antibody suppressed EAU despite maintained T-cell proliferation and IFN{gamma} production. Furthermore, locally administered DX109 monoclonal antibody resulted in an earlier resolution of disease. These experiments demonstrate that promoting CD200R-mediated signaling can successfully prevent full expression of IFN{gamma}-mediated macrophage activation and protect against tissue damage during autoimmune responses.
Original languageEnglish
Pages (from-to)580 - 598
Number of pages9
JournalAmerican Journal of Pathology
Volume171 (2)
DOIs
Publication statusPublished - Aug 2007

Bibliographical note

Publisher: American Society for Investigative Pathology

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