NADPH Oxidase p47phox-Mediated Auto-Inflammation and Autoimmunity

National Institute Of Allergy And Infectious Diseases

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Abstract

A current focus of this project is to characterize the aberrant function of antigen presenting cell (dendritic cells, macrophages) from p47phox-/- mice to understand the consequences in host defense against autoimmune disease. In addition to our investigations to systematically characterize p47phox-/- immune cell function, we have worked collaboratively with the NIAID comparative medicine branch to examine p47phox-/- mice for evidence of spontaneous systemic and organ specific autoreactive and autoimmune disease. Gross and histological analysis of 1 - 14 month old p47phox-/- mice showed that aging p47phox-/- mice develop a severe diffuse progressive macrophage pneumonia that is 100% fatal in mice that remain free of infection. The predominant lung lesion is the development of macrophage hyperplasia with intracellular eosinophilic crystals and a Chitinase-like protein (Ym1/Ym2). In addition spleen, LN and bone marrow macrophages also develop proliferative macrophage foci. We have also found that aging p47phox-/- mice develop a membranoproliferative glomerulonephritis, with T cell infiltrates, independent of the macrophage pneumonia.