title: Homeostatic regulation of Salmonella-induced mucosal inflammation and injury by IL-23.
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.
authors.affiliation: Department of Pathology and Program in Molecular and Cellular Biology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Muyiwa
authors.initials: M
authors.lastname: Awoniyi
authors.forename: Samuel I
authors.initials: SI
authors.lastname: Miller
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Wilson
authors.forename: Adeline M
authors.initials: AM
authors.lastname: Hajjar
authors.forename: Kelly D
authors.initials: KD
authors.lastname: Smith
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology*; D006706:Homeostasis / Q000276:immunology*; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D053760:Interleukin-23 Subunit p19 / Q000235:genetics / Q000276:immunology*; D007378:Interleukins / Q000235:genetics / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D018123:Receptors, Interleukin / Q000235:genetics / Q000276:immunology; D012480:Salmonella Infections / Q000276:immunology* / Q000473:pathology; D012486:Salmonella typhimurium / Q000276:immunology*; D000097043:Interleukin-22
chemical_list: D007371:Interferon-gamma; D018664:Interleukin-12; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D018123:Receptors, Interleukin; D000097043:Interleukin-22; C508527:Il17rc protein, mouse; C508841:Il23a protein, mouse