title: IL-23 and Th17 cells enhance Th2-cell-mediated eosinophilic airway inflammation in mice.
abstract: BACKGROUND
  The IL-23-IL-17A-producing CD4(+) T-cell (Th17 cell) axis plays an important role in the development of chronic inflammatory diseases, including autoimmune diseases. However, the role of the IL-23-Th17 cell axis in the regulation of allergic airway inflammation is still largely unknown.
  
  
  OBJECTIVE
  To determine the role of IL-23 and Th17 cells in allergic airway inflammation.
  
  
  METHODS
  We examined the effect of anti-IL-23 antibody on antigen-induced airway inflammation. We also investigated the effect of enforced expression of IL-23 on allergic airway inflammation by generating lung-specific IL-23 transgenic mice. Moreover, we examined the effect of adoptive transfer of antigen-specific Th17 cells on allergic airway inflammation.
  
  
  RESULTS
  IL-23 mRNA was expressed in the lung of sensitized mice upon antigen inhalation, and the neutralization of IL-23 decreased antigen-induced eosinophil recruitment and Th2 cytokine production in the airways. The enforced expression of IL-23 in the airways significantly enhanced antigen-induced eosinophil and neutrophil recruitment into the airways; Th2 cytokine, IL-17A, and tumor necrosis factor (TNF)-alpha production in the airways; goblet cell hyperplasia; and airway hyperresponsiveness. Moreover, IL-23-mediated enhancement of antigen-induced Th2 cytokine production and eosinophil recruitment in the airways was still observed in the mice lacking IL-17A. Furthermore, although adoptive transfer of antigen-specific Th17 cells alone induced neutrophil but not eosinophil recruitment into the airways upon antigen inhalation, cotransfer of Th17 cells with Th2 cells significantly enhanced antigen-induced Th2-cell-mediated eosinophil recruitment into the airways and airway hyperresponsiveness.
  
  
  CONCLUSIONS
  IL-23 and Th17 cells not only induce Th17-cell-mediated neutrophilic airway inflammation but also up-regulate Th2-cell-mediated eosinophilic airway inflammation.
authors.affiliation: Department of Allergy and Clinical Immunology, Chiba University Hospital, Chiba, Japan.
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Wakashin
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirose
authors.forename: Yuko
authors.initials: Y
authors.lastname: Maezawa
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Kagami
authors.forename: Akira
authors.initials: A
authors.lastname: Suto
authors.forename: Norihiko
authors.initials: N
authors.lastname: Watanabe
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Saito
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hatano
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tokuhisa
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Paolo
authors.initials: P
authors.lastname: Puccetti
authors.forename: Itsuo
authors.initials: I
authors.lastname: Iwamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakajima
mesh_terms: D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000276:immunology*; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology*; D053759:Interleukin-23 / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011014:Pneumonia / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D015854:Up-Regulation
chemical_list: D020381:Interleukin-17; D053759:Interleukin-23