title: IL-22-producing CD4+ cells are depleted in actively inflamed colitis tissue.
abstract: T helper type (Th17) cytokines such as interleukin (IL)-17A and IL-22 are important in maintaining mucosal barrier function and may be important in the pathogenesis of inflammatory bowel diseases (IBDs). Here, we analyzed cells from the colon of IBD patients and show that Crohn's disease (CD) patients had significantly elevated numbers of IL-17+, CD4+ cells compared with healthy controls and ulcerative colitis (UC) patients, but these numbers did not vary based on the inflammatory status of the mucosa. By contrast, UC patients had significantly reduced numbers of IL-22+ cells in actively inflamed tissues compared with both normal tissue and healthy controls. There was a selective increase in mono-IL-17-producing cells from the mucosa of UC patients with active inflammation together with increased expression of transforming growth factor (TGF)-β and c-Maf. Increasing concentrations of TGF-β in lamina propria mononuclear cell cultures significantly depleted Th22 cells, whereas anti-TGF-β antibodies increased IL-22 production. When mucosal microbiota was examined, depletion of Th22 cells in actively inflamed tissue was associated with reduced populations of Clostridiales and increased populations of Proteobacteria. These results suggest that increased TGF-β during active inflammation in UC may lead to the loss of Th22 cells in the human intestinal mucosa.
authors.affiliation: Division of Parasitology, Department of Microbiology, New York University School of Medicine, New York, New York, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Leung
authors.affiliation: Department of Medicine, New York University School of Medicine, New York, New York, USA.
authors.forename: M
authors.initials: M
authors.lastname: Davenport
authors.affiliation: 1] Department of Medicine, New York University School of Medicine, New York, New York, USA [2] VA New York Harbor Healthcare System, New York, New York, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Wolff
authors.affiliation: Division of Parasitology, Department of Microbiology, New York University School of Medicine, New York, New York, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Wiens
authors.affiliation: Department of Medicine, Division of Gastroenterology, Mount Sinai School of Medicine, New York, New York, USA.
authors.forename: W M
authors.initials: WM
authors.lastname: Abidi
authors.affiliation: 1] Department of Medicine, New York University School of Medicine, New York, New York, USA [2] VA New York Harbor Healthcare System, New York, New York, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Poles
authors.affiliation: 1] Department of Medicine, New York University School of Medicine, New York, New York, USA [2] VA New York Harbor Healthcare System, New York, New York, USA.
authors.forename: I
authors.initials: I
authors.lastname: Cho
authors.affiliation: Department of Medicine, Division of Gastroenterology, Mount Sinai School of Medicine, New York, New York, USA.
authors.forename: T
authors.initials: T
authors.lastname: Ullman
authors.affiliation: Immunology Institute, Mount Sinai School of Medicine, New York, New York, USA.
authors.forename: L
authors.initials: L
authors.lastname: Mayer
authors.affiliation: Division of Parasitology, Department of Microbiology, New York University School of Medicine, New York, New York, USA.
authors.forename: P
authors.initials: P
authors.lastname: Loke
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D007378:Interleukins / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D064307:Microbiota; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D007378:Interleukins; D016212:Transforming Growth Factor beta; D000097043:Interleukin-22