title: Homeostatic IL-23 receptor signaling limits Th17 response through IL-22-mediated containment of commensal microbiota.
abstract: Mammalian hosts are colonized with commensal microbes in various mucosal and epithelial tissues, including the intestinal tract. In mice, the presence of segmented filamentous bacteria (SFB) promotes Th17 differentiation and the development of autoimmune disease. Here, we demonstrate that the IL-23 pathway dynamically regulates the abundance of SFB as well as mucosal barrier function in the adult animal. Genetic or pharmacological inactivation of the pathway selectively perturbs the abundance of a small group of commensals, including SFB, and results in an impaired mucosal barrier. Defective barrier function leads to systemic dissemination of microbial products, provoking induction of the IL-23 pathway with dual consequences: IL-23 drives IL-22 production to reinforce mucosal barrier function and elicit antimicrobial activities, and it also drives the differentiation of Th17 cells in an attempt to combat escaped microbes in the lamina propria and in distal tissues. Thus, barrier defects generate a systemic environment that facilitates Th17 development.
authors.affiliation: Departments of Immunology.
authors.forename: Vincent Feng-Sheng
authors.initials: VF
authors.lastname: Shih
authors.affiliation: Departments of Immunology.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Cox
authors.affiliation: Molecular Biology, and.
authors.forename: Noelyn M
authors.initials: NM
authors.lastname: Kljavin
authors.affiliation: Departments of Immunology.
authors.forename: Hart S
authors.initials: HS
authors.lastname: Dengler
authors.affiliation: Pathology, Genentech, Inc., South San Francisco, CA 94080; and.
authors.forename: Mike
authors.initials: M
authors.lastname: Reichelt
authors.affiliation: Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, PA 15213.
authors.forename: Pawan
authors.initials: P
authors.lastname: Kumar
authors.affiliation: Pathology, Genentech, Inc., South San Francisco, CA 94080; and.
authors.forename: Linda
authors.initials: L
authors.lastname: Rangell
authors.affiliation: Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, PA 15213.
authors.forename: Jay K
authors.initials: JK
authors.lastname: Kolls
authors.affiliation: Pathology, Genentech, Inc., South San Francisco, CA 94080; and.
authors.forename: Lauri
authors.initials: L
authors.lastname: Diehl
authors.affiliation: Departments of Immunology.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Ouyang
authors.affiliation: Departments of Immunology, ghilardi@gene.com.
authors.forename: Nico
authors.initials: N
authors.lastname: Ghilardi
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D007378:Interleukins / Q000235:genetics / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D018345:Mice, Knockout; D064307:Microbiota / Q000276:immunology*; D018123:Receptors, Interleukin / Q000235:genetics / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D000097043:Interleukin-22
chemical_list: D007378:Interleukins; D018123:Receptors, Interleukin; D000097043:Interleukin-22; C528688:interleukin-23 receptor, mouse
keywords: endotoxemia; interleukin-17; microbiome; mucosal immunity