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Mary Dinauer, MD, PhD, studies the superoxide-generating leukocyte NADPH oxidase and the role of oxidant production by neutrophils and macrophages in microbial killing, the inflammatory response, and autoimmunity. Inactivating mutations in the NADPH oxidase result in chronic granulomatous disease (CGD), a primary immunodeficiency associated with recurrent bacterial and fungal infections as well as a variety of chronic inflammatory disorders, including inflammatory bowel disease and discoid lupus. Moreover, hypomorphic NADPH oxidase gene variants are now linked to inflammatory bowel disease and autoimmunity. These clinical manifestations reflect the dual importance of the NADPH oxidase both for microbial killing and for negatively regulating cellular processes that limit inflammation by redox mechanisms.
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