Homeostatic regulation of Salmonella-induced mucosal inflammation and injury by IL-23 |
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Authors: | Awoniyi Muyiwa Miller Samuel I Wilson Christopher B Hajjar Adeline M Smith Kelly D |
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Affiliation: | Department of Pathology and Program in Molecular and Cellular Biology, University of Washington, Seattle, Washington, United States of America. |
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Abstract: | IL-12 and IL-23 regulate innate and adaptive immunity to microbial pathogens through influencing the expression of IFN-γ, IL-17, and IL-22. Herein we define the roles of IL-12 and IL-23 in regulating host resistance and intestinal inflammation during acute Salmonella infection. We find that IL-23 alone is dispensable for protection against systemic spread of bacteria, but synergizes with IL-12 for optimal protection. IL-12 promotes the production of IFN-γ by NK cells, which is required for resistance against Salmonella and also for induction of intestinal inflammation and epithelial injury. In contrast, IL-23 controls the severity of inflammation by inhibiting IL-12A expression, reducing IFN-γ and preventing excessive mucosal injury. Our studies demonstrate that IL-23 is a homeostatic regulator of IL-12-dependent, IFN-γ-mediated intestinal inflammation. |
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