title: IL-22 Restrains Tapeworm-Mediated Protection against Experimental Colitis via Regulation of IL-25 Expression.
abstract: Interleukin (IL)-22, an immune cell-derived cytokine whose receptor expression is restricted to non-immune cells (e.g. epithelial cells), can be anti-inflammatory and pro-inflammatory. Mice infected with the tapeworm Hymenolepis diminuta are protected from dinitrobenzene sulphonic acid (DNBS)-induced colitis. Here we assessed expulsion of H. diminuta, the concomitant immune response and the outcome of DNBS-induced colitis in wild-type (WT) and IL-22 deficient mice (IL-22-/-) ± infection. Interleukin-22-/- mice had a mildly impaired ability to expel the worm and this correlated with reduced or delayed induction of TH2 immunity as measured by splenic and mesenteric lymph node production of IL-4, IL-5 and IL-13 and intestinal Muc-2 mRNA and goblet cell hyperplasia; in contrast, IL-25 increased in the small intestine of IL-22-/- mice 8 and 12 days post-infection compared to WT mice. In vitro experiments revealed that H. diminuta directly evoked epithelial production of IL-25 that was inhibited by recombinant IL-22. Also, IL-10 and markers of regulatory T cells were increased in IL-22-/- mice that displayed less DNBS (3 mg, ir. 72h)-induced colitis. Wild-type mice infected with H. diminuta were protected from colitis, as were infected IL-22-/- mice and the latter to a degree that they were almost indistinguishable from control, non-DNBS treated mice. Finally, treatment with anti-IL-25 antibodies exaggerated DNBS-induced colitis in IL-22-/- mice and blocked the anti-colitic effect of infection with H. diminuta. Thus, IL-22 is identified as an endogenous brake on helminth-elicited TH2 immunity, reducing the efficacy of expulsion of H. diminuta and limiting the effectiveness of the anti-colitic events mobilized following infection with H. diminuta in a non-permissive host.
authors.affiliation: Gastrointestinal Research Group, Department of Physiology and Pharmacology, Calvin, Joan and Phoebe Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: José L
authors.initials: JL
authors.lastname: Reyes
authors.affiliation: Gastrointestinal Research Group, Department of Physiology and Pharmacology, Calvin, Joan and Phoebe Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Maria R
authors.initials: MR
authors.lastname: Fernando
authors.affiliation: Gastrointestinal Research Group, Department of Physiology and Pharmacology, Calvin, Joan and Phoebe Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Fernando
authors.initials: F
authors.lastname: Lopes
authors.affiliation: Gastrointestinal Research Group, Department of Physiology and Pharmacology, Calvin, Joan and Phoebe Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Leung
authors.affiliation: Gastrointestinal Research Group, Department of Physiology and Pharmacology, Calvin, Joan and Phoebe Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Mancini
authors.affiliation: Gastrointestinal Research Group, Department of Physiology and Pharmacology, Calvin, Joan and Phoebe Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Chelsea E
authors.initials: CE
authors.lastname: Matisz
authors.affiliation: Gastrointestinal Research Group, Department of Physiology and Pharmacology, Calvin, Joan and Phoebe Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Arthur
authors.initials: A
authors.lastname: Wang
authors.affiliation: Gastrointestinal Research Group, Department of Physiology and Pharmacology, Calvin, Joan and Phoebe Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Derek M
authors.initials: DM
authors.lastname: McKay
mesh_terms: D000818:Animals; D003092:Colitis / Q000276:immunology*; D006925:Hymenolepiasis / Q000276:immunology*; D048190:Hymenolepis diminuta / Q000276:immunology*; D016753:Interleukin-10 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D007378:Interleukins / Q000235:genetics / Q000276:immunology*; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D000097043:Interleukin-22
chemical_list: D016753:Interleukin-10; D015847:Interleukin-4; D007378:Interleukins; D000097043:Interleukin-22; C556062:IL10 protein, mouse; C442281:Mydgf protein, mouse