title: IL-25 and IL-33 Contribute to Development of Eosinophilic Airway Inflammation in Epicutaneously Antigen-Sensitized Mice.
abstract: BACKGROUND
  IL-25, IL-33 and TSLP are produced predominantly by epithelial cells and are known to induce Th2-type cytokines. Th2-type cytokines are involved not only in host defense against nematodes, but also in the development of Th2-type allergic diseases. TSLP was reported to be crucial for development of allergic airway inflammation in mice after inhalation of allergens to which they had been sensitized epicutaneously (EC) beforehand. However, the roles of IL-25 and IL-33 in the setting remain unclear.
  
  
  METHODS
  Mice deficient in IL-25 and IL-33 were sensitized EC with ovalbumin (OVA) and then challenged intranasally with OVA. Airway inflammation, the number of inflammatory cells in bronchoalveolar lavage fluids (BALFs) and airway hyperresponsiveness (AHR) in the mice were determined, respectively, by histological analysis, with a hemocytometer, and by using plethysmograph chambers with a ventilator. Expression of mRNA in the skin and lungs was determined by quantitative PCR, while the BALF levels of myeloperoxidase (MPO) and eosinophil peroxidase (EPO) and the serum levels of IgE were determined by ELISA.
  
  
  RESULTS
  Normal OVA-specific Th2- and Th17-cell responses of lymph nodes and spleens were observed in IL-25-deficient (IL-25-/-) and IL-33-/- mice after EC sensitization with OVA. Nevertheless, the number of eosinophils, but not neutrophils, in the BALFs, and the levels of Th2 cytokines, but not Th17 cytokines, in the lungs were significantly decreased in the IL-25-/- and IL-33-/- mice pre-sensitized EC with OVA, followed by inhalation of OVA, whereas their levels of AHR and OVA-specific serum IgE were normal.
  
  
  CONCLUSIONS
  Both IL-25 and IL-33 are critical for induction of Th2-type cytokine-mediated allergic airway eosinophilia, but not Th17-type cytokine-mediated airway neutrophilia, at the local sites of lungs in the challenge phase of mice sensitized EC with OVA. They do not affect OVA-specific T-cell induction in the sensitization phase.
authors.affiliation: Department of Pediatrics, Keio University School of Medicine, Tokyo, 160-8582, Japan; Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Morita
authors.affiliation: Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan; Department of Immunology, Faculty of Health Science, Kyorin University, Tokyo, 192-8508, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Arae
authors.affiliation: Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan; Department of Pediatrics, Jikei University School of Medicine, Tokyo 105-8461, Japan.
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Unno
authors.affiliation: Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
authors.forename: Sumika
authors.initials: S
authors.lastname: Toyama
authors.affiliation: Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Motomura
authors.affiliation: Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Matsuda
authors.affiliation: Atopy Research Center, Juntendo University School of Medicine, Tokyo, 113-8412, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Suto
authors.affiliation: Atopy Research Center, Juntendo University School of Medicine, Tokyo, 113-8412, Japan.
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.affiliation: Animal Research Center, Tokyo Medical University, Tokyo 160-8402, Japan.
authors.forename: Katsuko
authors.initials: K
authors.lastname: Sudo
authors.affiliation: Department of Pediatrics, Keio University School of Medicine, Tokyo, 160-8582, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Saito
authors.affiliation: Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan; Atopy Research Center, Juntendo University School of Medicine, Tokyo, 113-8412, Japan; Laboratory of Systems Biology, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan; Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency, Saitama 332-0012, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakae
mesh_terms: D000818:Animals; D004804:Eosinophils / Q000473:pathology*; D020381:Interleukin-17 / Q000502:physiology*; D000067596:Interleukin-33 / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000473:pathology
chemical_list: D020381:Interleukin-17; D000067596:Interleukin-33; D010047:Ovalbumin