Innate and adaptive interleukin-22 protects mice from inflammatory bowel disease.
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.
Zenewicz
Lauren A
LA
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520 USA.
Yancopoulos
George D
GD
Valenzuela
David M
DM
Murphy
Andrew J
AJ
Stevens
Sean
S
Flavell
Richard A
RA
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
D016207:Cytokines; D018398:Homeodomain Proteins; D007378:Interleukins; D011994:Recombinant Proteins; D000097043:Interleukin-22; C064658:RAG-1 protein