Journal
AMERICAN JOURNAL OF PATHOLOGY
Volume 171, Issue 2, Pages 580-588Publisher
AMER SOC INVESTIGATIVE PATHOLOGY, INC
DOI: 10.2353/ajpath.2007.070272
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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.
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