title: IL-25 enhances allergic airway inflammation by amplifying a TH2 cell-dependent pathway in mice.
abstract: BACKGROUND
  A novel IL-17 family cytokine, IL-25, has been reported to induce IL-4, IL-5, and IL-13 production from undefined non-T/non-B cells and then induce T(H)2-type immune responses. However, the roles of IL-25 in inducing allergic airway inflammation remain unknown.
  
  
  OBJECTIVE
  We sought to determine whether IL-25 is involved in causing allergic airway inflammation.
  
  
  METHODS
  We examined the expression of IL-25 mRNA in the lungs of sensitized mice on antigen inhalation. We also examined the effect of IL-25 neutralization by soluble IL-25 receptor on antigen-induced airway inflammation. We then generated IL-25 transgenic mice that express IL-25 specifically in the lung under the control of the Clara cells-10-kd protein promoter and investigated the effect of enforced IL-25 expression on antigen-induced airway inflammation.
  
  
  RESULTS
  IL-25 mRNA was expressed in the lungs of sensitized mice on antigen inhalation, and the neutralization of IL-25 by soluble IL-25 receptor decreased antigen-induced eosinophil and CD4(+) T-cell recruitment into the airways. The enforced expression of IL-25 in the lung itself failed to induce allergic airway inflammation, whereas the expression of IL-25 significantly enhanced antigen-induced T(H)2 cytokine production, eosinophil and CD4(+) T cell recruitment, and goblet cell hyperplasia in the airways. Moreover, IL-25-induced enhancement of allergic airway inflammation was inhibited by the depletion of CD4(+) T cells or by the absence of signal transducer and activator of transcription 6.
  
  
  CONCLUSIONS
  IL-25 enhances antigen-induced allergic airway inflammation by amplifying a T(H)2 cell-dependent pathway.
  
  
  CONCLUSIONS
  IL-25 might be involved in the enhancement, prolongation, or both of T(H)2 cell-mediated allergic diseases, such as asthma.
authors.affiliation: Department of Allergy and Clinical Immunology, Clinical Cell Biology, Graduate School of Medicine, Chiba University, Chiba City, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Tamachi
authors.forename: Yuko
authors.initials: Y
authors.lastname: Maezawa
authors.forename: Kei
authors.initials: K
authors.lastname: Ikeda
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Kagami
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hatano
authors.forename: Yohei
authors.initials: Y
authors.lastname: Seto
authors.forename: Akira
authors.initials: A
authors.lastname: Suto
authors.forename: Kotaro
authors.initials: K
authors.lastname: Suzuki
authors.forename: Norihiko
authors.initials: N
authors.lastname: Watanabe
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Saito
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tokuhisa
authors.forename: Itsuo
authors.initials: I
authors.lastname: Iwamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakajima
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000235:genetics / Q000502:physiology*; D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology; D000818:Animals; D006801:Humans; D007117:Immunization, Secondary; D018836:Inflammation Mediators / Q000502:physiology*; D020381:Interleukin-17; D007378:Interleukins / Q000009:adverse effects / Q000235:genetics / Q000502:physiology*; D007840:Latex / Q000008:administration & dosage / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*
chemical_list: D000276:Adjuvants, Immunologic; D000485:Allergens; C486701:IL25 protein, human; D018836:Inflammation Mediators; D020381:Interleukin-17; D007378:Interleukins; D007840:Latex; D012333:RNA, Messenger; D010047:Ovalbumin