title: Atopy and Inhaled Corticosteroid Use Associate with Fewer IL-17+ Cells in Asthmatic Airways.
abstract: BACKGROUND
  Interleukin (IL)-17 plays a critical role in numerous immune and inflammatory responses and was recently suggested to contribute to the pathogenesis of nonatopic (non-eosinophil/neutrophil-dominant) asthma. We aimed to compare expression of IL-17 in bronchial airways between atopic and nonatopic asthmatics, with/without inhaled corticosteroid (ICS) use and to identify its major cellular source.
  
  
  METHODS
  Bronchial biopsies from 114 patients with mild-to-moderate asthma were investigated: 33 nonatopic, 63 non-corticosteroid users, 90 nonsmokers. IL-17 expression was correlated with atopy and inflammatory cell counts (EPX, NP57, CD3, CD4, CD8, CD20, CD68), taking ICS use and smoking into account. Multiple linear regression analyses were used to determine the independent factors as well as the most relevant inflammatory cells contributing to IL-17 expression. Double immunostainings were performed to confirm the major cellular source of IL-17.
  
  
  RESULTS
  In non-ICS users, nonatopic asthmatics had more IL-17+ cells in the airway wall than atopic asthmatics. In both atopic and nonatopic asthmatics, ICS use was associated with lower numbers of IL-17+ cells, independent of smoking. The number of IL-17+ cells was associated with the number of neutrophils (B: 0.26, 95% CI: 0.17-0.35) and eosinophils (B: 0.18, 95% CI: 0.07-0.29). The majority of IL-17+ cells were neutrophils, as confirmed by double immunostaining.
  
  
  CONCLUSIONS
  We show for the first time that atopy and ICS use are associated with lower numbers of IL-17+ cells in asthmatic airways. Importantly, IL-17+ cells were mostly neutrophils which conflicts with the paradigm that lymphocytes (Th17) are the main source of IL-17.
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Pulmonology, Groningen, the Netherlands.|University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, the Netherlands.|University of Groningen, University Medical Center Groningen, Research Institute for Asthma and COPD (GRIAC), Groningen, the Netherlands.|Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Fattahi
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, the Netherlands.|University of Groningen, University Medical Center Groningen, Research Institute for Asthma and COPD (GRIAC), Groningen, the Netherlands.
authors.forename: Corry-Anke
authors.initials: CA
authors.lastname: Brandsma
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, the Netherlands.|University of Groningen, University Medical Center Groningen, Research Institute for Asthma and COPD (GRIAC), Groningen, the Netherlands.
authors.forename: Monique
authors.initials: M
authors.lastname: Lodewijk
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, the Netherlands.|University of Groningen, University Medical Center Groningen, Research Institute for Asthma and COPD (GRIAC), Groningen, the Netherlands.
authors.forename: Marjan
authors.initials: M
authors.lastname: Reinders-Luinge
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Pulmonology, Groningen, the Netherlands.|University of Groningen, University Medical Center Groningen, Research Institute for Asthma and COPD (GRIAC), Groningen, the Netherlands.
authors.forename: Dirkje S
authors.initials: DS
authors.lastname: Postma
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, the Netherlands.|University of Groningen, University Medical Center Groningen, Research Institute for Asthma and COPD (GRIAC), Groningen, the Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Timens
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, the Netherlands.|University of Groningen, University Medical Center Groningen, Research Institute for Asthma and COPD (GRIAC), Groningen, the Netherlands.
authors.forename: Machteld N
authors.initials: MN
authors.lastname: Hylkema
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Pulmonology, Groningen, the Netherlands.|University of Groningen, University Medical Center Groningen, Research Institute for Asthma and COPD (GRIAC), Groningen, the Netherlands.
authors.forename: Nick H T
authors.initials: NH
authors.lastname: Ten Hacken
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000009:adverse effects; D000328:Adult; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D001706:Biopsy; D001980:Bronchi / Q000187:drug effects / Q000473:pathology; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D020381:Interleukin-17 / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D012138:Respiratory Therapy / Q000009:adverse effects*; D058504:Th17 Cells / Q000276:immunology
chemical_list: D000305:Adrenal Cortex Hormones; D020381:Interleukin-17