title: IL-22-producing neutrophils contribute to antimicrobial defense and restitution of colonic epithelial integrity during colitis.
abstract: IL-22 plays an important role in mucosal epithelial cell homeostasis. Using a dextran sodium sulfate-induced mouse model of acute colitis, we observed an IL-23-dependent up-regulation of IL-22 in the middle and distal colon at the onset of epithelial cell damage. This heightened IL-22 correlated with an influx of innate immune cells, suggesting an important role in colonic epithelial protection. Freshly isolated colon-infiltrating neutrophils produced IL-22 contingent upon IL-23 signaling, and IL-22 production was augmented by TNF-α. Importantly, the depletion of neutrophils resulted in diminished IL-22 levels in the colon, and the transfer of IL-22-competent neutrophils to Il22a-deficient mice protected the colonic epithelium from dextran sodium sulfate-induced damage. In addition, IL-22-producing neutrophils targeted colonic epithelial cells to up-regulate the antimicrobial peptides, RegIIIβ and S100A8. This study establishes a role for neutrophils in providing IL-22-dependent mucosal epithelial support that contributes to the resolution of colitis.
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Carlene L
authors.initials: CL
authors.lastname: Zindl
authors.forename: Jen-Feng
authors.initials: JF
authors.lastname: Lai
authors.forename: Yun Kyung
authors.initials: YK
authors.lastname: Lee
authors.forename: Craig L
authors.initials: CL
authors.lastname: Maynard
authors.forename: Stacey N
authors.initials: SN
authors.lastname: Harbour
authors.forename: Wenjun
authors.initials: W
authors.lastname: Ouyang
authors.forename: David D
authors.initials: DD
authors.lastname: Chaplin
authors.forename: Casey T
authors.initials: CT
authors.lastname: Weaver
mesh_terms: D000818:Animals; D040501:Calgranulin A / Q000235:genetics / Q000276:immunology; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D003106:Colon / Q000276:immunology* / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D053759:Interleukin-23 / Q000235:genetics / Q000276:immunology; D007378:Interleukins / Q000235:genetics / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000276:immunology; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D040501:Calgranulin A; D016264:Dextran Sulfate; D053759:Interleukin-23; D007378:Interleukins; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins; D000097043:Interleukin-22; C490253:Reg3b protein, mouse; C086145:S100a8 protein, mouse
keywords: interleukin-22; intestinal inflammation; leukocytes