homeostatic regulation of salmonella-induced mucosal inflammation and injury by il-23体内平衡调节salmonella-induced il-23粘膜炎症和损伤.pdfVIP

Homeostatic Regulation of Salmonella-Induced Mucosal Inflammation and Injury by IL-23 1 2 3¤ 4. 1 . Muyiwa Awoniyi , Samuel I. Miller , Christopher B. Wilson , Adeline M. Hajjar , Kelly D. Smith * 1 Department of Pathology and Program in Molecular and Cellular Biology, University of Washington, Seattle, Washington, United States of America, 2 Departments of Medicine, Genome Sciences and Microbiology, University of Washington, Seattle, Washington, United States of America, 3 Department of Immunology, University of Washington, Seattle, Washington, United States of America, 4 Department of Comparative Medicine, University of Washington, Seattle, Washington, United States of America Abstract IL-12 and IL-23 regulate innate and adaptive immunity to microbial pathogens through influencing the expression of IFN-c, 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-c 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-c and preventing excessive mucosal injury. Our studies demonstrate that IL-23 is a homeostatic regulator of IL-12-dependent, IFN-c-mediated intestinal inflammation. Citation: Awoniyi M, Miller SI, Wilso