title: Epithelial cell-derived IL-25, but not Th17 cell-derived IL-17 or IL-17F, is crucial for murine asthma.
abstract: IL-17A, IL-17F, and IL-25 are ligands for IL-17RA. In the current study, we demonstrated that IL-25-deficient mice-but not IL-17A-, IL-17F-, IL-17A/F-, IL-23p19-, or retinoic acid-related orphan receptor (ROR)-γt-deficient mice-showed significant suppression of 1) the number of eosinophils and the levels of proinflammatory mediators in bronchoalveolar lavage fluids, 2) airway hyperresponsiveness to methacholine, and 3) OVA-specific IgG1 and IgE levels in the serum during OVA-induced Th2-type/eosinophilic airway inflammation. The IL-25 deficiency did not affect lung dendritic cell migration or Ag-specific memory-Th2 cell expansion during Ag sensitization. Adoptive transfer of T cells, mast cells, or bone marrow cells from IL-25-deficient mice revealed that induction of Th2-type/eosinophilic airway inflammation was dependent on activation of lung epithelial cells and eosinophils by IL-25 produced by airway structural cells such as epithelial cells but not by such hematopoietic stem-cell-origin immune cells as T cells and mast cells. Therefore, airway structural cell-derived IL-25-rather than Th17 cell-derived IL-17A and IL-17F-is responsible for induction of local inflammation by promoting activation of lung epithelial cells and eosinophils in the elicitation phase of Th2-type/eosinophilic airway inflammation. It is not required for Ag-specific Th2 cell differentiation in the sensitization phase.
authors.affiliation: Department of Internal Medicine, Teikyo University School of Medicine, Tokyo 173-8605, Japan.
authors.forename: Maho
authors.initials: M
authors.lastname: Suzukawa
authors.forename: Hideaki
authors.initials: H
authors.lastname: Morita
authors.forename: Aya
authors.initials: A
authors.lastname: Nambu
authors.forename: Ken
authors.initials: K
authors.lastname: Arae
authors.forename: Eri
authors.initials: E
authors.lastname: Shimura
authors.forename: Akiko
authors.initials: A
authors.lastname: Shibui
authors.forename: Sachiko
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Keigo
authors.initials: K
authors.lastname: Suzukawa
authors.forename: Wakako
authors.initials: W
authors.lastname: Nakanishi
authors.forename: Keisuke
authors.initials: K
authors.lastname: Oboki
authors.forename: Naoki
authors.initials: N
authors.lastname: Kajiwara
authors.forename: Tatsukuni
authors.initials: T
authors.lastname: Ohno
authors.forename: Akina
authors.initials: A
authors.lastname: Ishii
authors.forename: Heinrich
authors.initials: H
authors.lastname: Körner
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Cua
authors.forename: Hajime
authors.initials: H
authors.lastname: Suto
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yoshimoto
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yamasoba
authors.forename: Ken
authors.initials: K
authors.lastname: Ohta
authors.forename: Katsuko
authors.initials: K
authors.lastname: Sudo
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Saito
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.forename: David H
authors.initials: DH
authors.lastname: Broide
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakae
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D018836:Inflammation Mediators / Q000502:physiology*; D020381:Interleukin-17 / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D007378:Interleukins / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: C515932:Il17f protein, mouse; D018836:Inflammation Mediators; D020381:Interleukin-17; D007378:Interleukins; C442281:Mydgf protein, mouse