title: ST2 requires Th2-, but not Th17-, type airway inflammation in epicutaneously antigen- sensitized mice.
abstract: BACKGROUND
  IL-33 is known to induce Th2-type cytokine production by various types of cells through its receptors, ST2 and IL-1RAcP. Polymorphism in the ST2 and/or IL-33 genes was found in patients with atopic dermatitis and asthma, implying that the IL-33/ST2 pathway is closely associated with susceptibility to these diseases. Exposure to allergens through damaged skin is suspected to be a trigger for allergen sensitization, resulting in development of such allergic disorders as asthma and atopic dermatitis.
  
  
  METHODS
  To elucidate the role(s) of the IL-33/ST2 pathway in asthma in individuals who had been epicutaneously sensitized to an antigen, wild-type and ST2-/- mice were epicutaneously sensitized with ovalbumin (OVA) and then were intranasally challenged with OVA. The degree of airway inflammation, the number of leukocytes and the activities of myeloperoxidase (MPO) and eosinophil peroxidase (EPO) in bronchoalveolar lavage fluids (BALFs), The levels of cytokines and chemokines in lungs and OVA-specific IgE levels in sera were determined by histological analysis, a hemocytometer, colorimetric assay, quantitative PCR or ELISA, respectively.
  
  
  RESULTS
  The number of eosinophils in BALFs, the levels of Th2 cytokines and chemoattractants in the lungs and OVA-specific IgE in sera from ST2-/- mice were significantly reduced compared with wild-type mice. Although the number of neutrophils in BALFs and the pulmonary levels of IL-17 were comparable in both mice, the levels of MPO activity in BALFs and neutrophil chemoattractants in the lung were reduced in ST2-/- mice.
  
  
  CONCLUSIONS
  The IL-33/ST2 pathway is crucial for Th2-cytokine-mediated eosinophilic, rather than Th17-cytokine-mediated neutrophilic, airway inflammation in mice that had been epicutaneously sensitized with antigens and then challenged with antigen.
authors.affiliation: Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Morita
authors.forename: Ken
authors.initials: K
authors.lastname: Arae
authors.forename: Tatsukuni
authors.initials: T
authors.lastname: Ohno
authors.forename: Naoki
authors.initials: N
authors.lastname: Kajiwara
authors.forename: Keisuke
authors.initials: K
authors.lastname: Oboki
authors.forename: Akio
authors.initials: A
authors.lastname: Matsuda
authors.forename: Hajime
authors.initials: H
authors.lastname: Suto
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.forename: Katsuko
authors.initials: K
authors.lastname: Sudo
authors.forename: Takao
authors.initials: T
authors.lastname: Takahashi
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakae
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D001249:Asthma / Q000276:immunology*; D004195:Disease Models, Animal; D004804:Eosinophils / Q000473:pathology; D006801:Humans; D007114:Immunization; D007073:Immunoglobulin E / Q000097:blood; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage; D009195:Peroxidase / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology*; D018123:Receptors, Interleukin / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D058504:Th17 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: C486189:Il1rl1 protein, mouse; C506535:Il33 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins; D018123:Receptors, Interleukin; D007073:Immunoglobulin E; D010047:Ovalbumin; D009195:Peroxidase