title: IL-22 attenuates IL-25 production by lung epithelial cells and inhibits antigen-induced eosinophilic airway inflammation.
abstract: BACKGROUND
  IL-22 functions as both a proinflammatory cytokine and an anti-inflammatory cytokine in various inflammations, depending on the cellular and cytokine milieu. However, the roles of IL-22 in the regulation of allergic airway inflammation are still largely unknown.
  
  
  OBJECTIVE
  We sought to determine whether IL-22 is involved in the regulation of allergic airway inflammation.
  
  
  METHODS
  We examined IL-22 production and its cellular source at the site of antigen-induced airway inflammation in mice. We also examined the effect of IL-22 neutralization, as well as IL-22 administration, on antigen-induced airway inflammation. We finally examined the effect of IL-22 on IL-25 production from a lung epithelial cell line (MLE-15 cells).
  
  
  RESULTS
  Antigen inhalation induced IL-22 production in the airways of sensitized mice. CD4(+) T cells, but not other lymphocytes or innate cells, infiltrating in the airways produced IL-22, and one third of IL-22-producing CD4(+) T cells also produced IL-17A. The neutralization of IL-22 by anti-IL-22 antibody enhanced antigen-induced IL-13 production, eosinophil recruitment, and goblet cell hyperplasia in the airways. On the other hand, intranasal administration of recombinant IL-22 attenuated antigen-induced eosinophil recruitment into the airways. Moreover, anti-IL-22 antibody enhanced antigen-induced IL-25 production in the airways, and anti-IL-25 antibody reversed the enhancing effect of anti-IL-22 antibody on antigen-induced eosinophil recruitment into the airways. Finally, IL-22 inhibited IL-13-mediated enhancement of IL-25 expression in IL-1β- or LPS-stimulated MLE-15 cells.
  
  
  CONCLUSIONS
  IL-22 attenuates antigen-induced airway inflammation, possibly by inhibiting IL-25 production by lung epithelial cells.
authors.affiliation: Department of Molecular Genetics, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Takahashi
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirose
authors.forename: Saki
authors.initials: S
authors.lastname: Kawashima
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Niwa
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Wakashin
authors.forename: Arifumi
authors.initials: A
authors.lastname: Iwata
authors.forename: Koji
authors.initials: K
authors.lastname: Tokoyoda
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Renauld
authors.forename: Itsuo
authors.initials: I
authors.lastname: Iwamoto
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakajima
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000276:immunology* / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism; D007150:Immunohistochemistry; D007378:Interleukins / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011014:Pneumonia / Q000276:immunology* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020545:Respiratory Mucosa / Q000276:immunology* / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D007378:Interleukins; D000097043:Interleukin-22; C442281:Mydgf protein, mouse