title: Dual Role of IL-22 in allergic airway inflammation and its cross-talk with IL-17A.
abstract: BACKGROUND
  IL-22 has both proinflammatory and antiinflammatory properties. Its role in allergic lung inflammation has not been explored.
  
  
  OBJECTIVE
  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.
  
  
  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.affiliation: Université de Orléans and CNRS-UMR6218, Molecular Immunology and Embryology, 3B Rue de la Férollerie, 45071 Orléans Cedex 2, France.
authors.forename: Anne-Gaelle
authors.initials: AG
authors.lastname: Besnard
authors.forename: Robert
authors.initials: R
authors.lastname: Sabat
authors.forename: Laure
authors.initials: L
authors.lastname: Dumoutier
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Renauld
authors.forename: Monique
authors.initials: M
authors.lastname: Willart
authors.forename: Bart
authors.initials: B
authors.lastname: Lambrecht
authors.forename: Mauro M
authors.initials: MM
authors.lastname: Teixeira
authors.forename: Sabine
authors.initials: S
authors.lastname: Charron
authors.forename: Lizette
authors.initials: L
authors.lastname: Fick
authors.forename: François
authors.initials: F
authors.lastname: Erard
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Warszawska
authors.forename: Kerstin
authors.initials: K
authors.lastname: Wolk
authors.forename: Valerie
authors.initials: V
authors.lastname: Quesniaux
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ryffel
authors.forename: Dieudonnée
authors.initials: D
authors.lastname: Togbe
mesh_terms: D000818:Animals; D001249:Asthma / Q000097:blood / Q000276:immunology*; D018925:Chemokines / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology*; D007378:Interleukins / Q000097:blood / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D018418:Th2 Cells / Q000276:immunology; D000097043:Interleukin-22
chemical_list: D018925:Chemokines; D016207:Cytokines; D020381:Interleukin-17; D007378:Interleukins; D000097043:Interleukin-22