title: Epithelial interleukin-25 is a key mediator in Th2-high, corticosteroid-responsive asthma.
abstract: BACKGROUND
  Activation of type 2 cytokine pathways plays a central role in a large subset of subjects with asthma. Th2-high and Th2-low asthma have distinct clinical, pathologic, and molecular phenotypes and respond differently to therapy. The factors that initiate type 2 responses in some subjects with asthma are unknown.
  
  
  OBJECTIVE
  To determine whether expression of epithelial cytokines IL-25, IL-33, and thymic stromal lymphopoietin are associated with type 2 responses and predict response to inhaled corticosteroid (ICS) in asthma.
  
  
  METHODS
  We analyzed pulmonary function tests, blood, and bronchoscopic biopsies from 21 healthy control subjects and 43 subjects with asthma. Subjects with asthma underwent an 8-week treatment with inhaled budesonide.
  
  
  RESULTS
  Epithelial expression of IL-25, but not IL-33 or thymic stromal lymphopoietin, was increased in a subset of subjects with asthma. The IL-25-high subset had greater airway hyperresponsiveness, more airway and blood eosinophils, higher serum IgE, more subepithelial thickening, and higher expression of Th2 signature genes. ICS improved FEV1 and hyperresponsiveness in the IL-25-high but not the IL-25-low subset. Plasma IL-25 levels correlated with epithelial IL-25 expression, airway eosinophilia, and beneficial responses to ICS treatment.
  
  
  CONCLUSIONS
  IL-25 measurements identify two subsets of subjects with distinct asthma phenotypes and different responses to ICS. Because IL-25 has a major role in triggering type 2 responses, bronchial epithelial IL-25 expression is likely a key determinant of type 2 response activation in asthma. Plasma IL-25 level reflects airway IL-25/type 2 response activation and may be useful for predicting responses to asthma therapy.
authors.affiliation: 1 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, and.
authors.forename: Dan
authors.initials: D
authors.lastname: Cheng
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xue
authors.forename: Lingling
authors.initials: L
authors.lastname: Yi
authors.forename: Huimin
authors.initials: H
authors.lastname: Shi
authors.forename: Kan
authors.initials: K
authors.lastname: Zhang
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Huo
authors.forename: Luke R
authors.initials: LR
authors.lastname: Bonser
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhao
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Xu
authors.forename: David J
authors.initials: DJ
authors.lastname: Erle
authors.forename: Guohua
authors.initials: G
authors.lastname: Zhen
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D000067596:Interleukin-33; D007378:Interleukins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018418:Th2 Cells / Q000378:metabolism*; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D016207:Cytokines; C486701:IL25 protein, human; C506536:IL33 protein, human; D020381:Interleukin-17; D000067596:Interleukin-33; D007378:Interleukins; D000094632:Thymic Stromal Lymphopoietin
keywords: IL-25; asthma; phenotype