title: Innate and adaptive interleukin-22 protects mice from inflammatory bowel disease.
abstract: Inflammatory bowel disease (IBD) is a chronic inflammatory disease thought to be mediated by dysfunctional innate and/or adaptive immunity. This aberrant immune response leads to the secretion of harmful cytokines that destroy the epithelium of the gastrointestinal tract and thus cause further inflammation. Interleukin-22 (IL-22) is a T helper 17 (Th17) T cell-associated cytokine that is bifunctional in that it has both proinflammatory and protective effects on tissues depending on the inflammatory context. We show herein that IL-22 protected mice from IBD. Interestingly, not only was this protection mediated by CD4+ T cells, but IL-22-expressing natural killer (NK) cells also conferred protection. In addition, IL-22 expression was differentially regulated between NK cell subsets. Thus, both the innate and adaptive immune responses have developed protective mechanisms to counteract the damaging effects of inflammation on tissues.
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520 USA.
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Zenewicz
authors.forename: George D
authors.initials: GD
authors.lastname: Yancopoulos
authors.forename: David M
authors.initials: DM
authors.lastname: Valenzuela
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Murphy
authors.forename: Sean
authors.initials: S
authors.lastname: Stevens
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D003092:Colitis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D003106:Colon / Q000276:immunology; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007110:Immunity, Active; D007113:Immunity, Innate; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007378:Interleukins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D016207:Cytokines; D018398:Homeodomain Proteins; D007378:Interleukins; D011994:Recombinant Proteins; D000097043:Interleukin-22; C064658:RAG-1 protein