RATIONALE: IL-22 has both proinflammatory and antiinflammatory properties. Its role in allergic lung inflammation has not been explored. OBJECTIVES: To investigate the expression and roles of IL-22 in the onset and resolution of experimental allergic asthma and its cross-talk with IL-17A. METHODS: IL-22 expression was assessed in patient samples and in the lung of mice immunized and challenged with ovalbumin. IL-22 functions in allergic airway inflammation were evaluated using mice deficient in IL-22 or anti-IL-22 neutralizing antibodies. Moreover, the effects of recombinant IL-22 and IL-17A neutralizing antibodies were investigated. MEASUREMENTS AND MAIN RESULTS: Increased pulmonary IL-22 expression is found in the serum of patients with asthma and mice immunized and challenged with ovalbumin. Allergic lung inflammation is IL-22 dependent because eosinophil recruitment, Th2 cytokine including IL-13 and IL-33, chemokine production, airway hyperreactivity, and mucus production are drastically reduced in mice deficient in IL-22 or by IL-22 antibody neutralization during immunization of wild-type mice. By contrast, IL-22 neutralization during antigen challenge enhanced allergic lung inflammation with increased Th2 cytokines. Consistent with this, recombinant IL-22 given with allergen challenge protects mice from lung inflammation. Finally, IL-22 may regulate the expression and proinflammatory properties of IL-17A in allergic lung inflammation. CONCLUSIONS: IL-22 is required for the onset of allergic asthma, but functions as a negative regulator of established allergic inflammation. Our study reveals that IL-22 contributes to the proinflammatory properties of IL-17A in experimental allergic asthma.
RATIONALE: IL-22 has both proinflammatory and antiinflammatory properties. Its role in allergic lung inflammation has not been explored. OBJECTIVES: To investigate the expression and roles of IL-22 in the onset and resolution of experimental allergic asthma and its cross-talk with IL-17A. METHODS:IL-22 expression was assessed in patient samples and in the lung of mice immunized and challenged with ovalbumin. IL-22 functions in allergic airway inflammation were evaluated using mice deficient in IL-22 or anti-IL-22 neutralizing antibodies. Moreover, the effects of recombinant IL-22 and IL-17A neutralizing antibodies were investigated. MEASUREMENTS AND MAIN RESULTS: Increased pulmonary IL-22 expression is found in the serum of patients with asthma and mice immunized and challenged with ovalbumin. Allergic lung inflammation is IL-22 dependent because eosinophil recruitment, Th2 cytokine including IL-13 and IL-33, chemokine production, airway hyperreactivity, and mucus production are drastically reduced in mice deficient in IL-22 or by IL-22 antibody neutralization during immunization of wild-type mice. By contrast, IL-22 neutralization during antigen challenge enhanced allergic lung inflammation with increased Th2 cytokines. Consistent with this, recombinant IL-22 given with allergen challenge protects mice from lung inflammation. Finally, IL-22 may regulate the expression and proinflammatory properties of IL-17A in allergic lung inflammation. CONCLUSIONS:IL-22 is required for the onset of allergic asthma, but functions as a negative regulator of established allergic inflammation. Our study reveals that IL-22 contributes to the proinflammatory properties of IL-17A in experimental allergic asthma.
Authors: Ana Paula Moreira; Karen A Cavassani; Ugur B Ismailoglu; Rikki Hullinger; Michael P Dunleavy; Darryl A Knight; Steven L Kunkel; Satoshi Uematsu; Shizuo Akira; Cory M Hogaboam Journal: J Clin Invest Date: 2011-10-17 Impact factor: 14.808
Authors: David W Draper; Kymberly M Gowdy; Jennifer H Madenspacher; Rhonda H Wilson; Gregory S Whitehead; Hideki Nakano; Arun R Pandiri; Julie F Foley; Alan T Remaley; Donald N Cook; Michael B Fessler Journal: J Immunol Date: 2012-04-25 Impact factor: 5.422