title: The Th17 pathway in cystic fibrosis lung disease.
abstract: BACKGROUND
  Cystic fibrosis (CF) is characterized by bronchoalveolar neutrophilia and submucosal lymphocytosis. We hypothesized that Th17 lymphocytes are part of this submucosal infiltrate.
  
  
  OBJECTIVE
  Quantification and phenotyping of the lymphocytic infiltrate in the bronchial submucosa of patients with CF (n = 53, of which 20 were newly diagnosed), non-CF bronchiectasis (n = 17), and healthy control subjects (n = 13).
  
  
  METHODS
  We measured IL-17 levels in bronchoalveolar lavage and CD4(+), CD8(+), and IL-17(+) cell counts in endobronchial biopsies. Correlations were made with infection status and other inflammatory markers. Potential cellular sources of IL-17 were determined by double staining.
  
  
  RESULTS
  IL-17(+) cell counts (median [interquartile range] cells/mm(2)) were significantly higher in patients with established CF (205 [115-551]) and non-CF bronchiectasis (245 [183-436]) than in control subjects (53 [12-82]) (P < 0.01 for both). Patients with newly diagnosed CF had intermediate counts (171 [91-252]). IL-17-positive CD4(+) T cells, γδT cells, natural killer T cells, and neutrophils were identified. Bronchoalveolar lavage IL-17 levels (pg/ml) were highest in established CF (14.6 [2.2-38.4]), low in newly diagnosed CF and control subjects (1.7 [1.7-1.74]; 1.7 [1.7-3]), and intermediate in non-CF bronchiectasis (9.1 [1.7-34] pg/ml) (Kruskal-Wallis P = 0.001). There was a significant correlation between IL-17 and neutrophil counts (P < 0.001, R = 0.6) as well as IL-4 (P < 0.001, R = 0.84).
  
  
  CONCLUSIONS
  Th17 lymphocytes are present in the airway submucosa in CF, even in a young, newly diagnosed group. Other IL-17(+) cells include neutrophils, γδ T cells, and natural killer T cells.
authors.affiliation: Department of Paediatric Respiratory Medicine, Royal Brompton Hospital, London, UK. hlt20@doctors.org.uk
authors.forename: Hui-Leng
authors.initials: HL
authors.lastname: Tan
authors.forename: Nicolas
authors.initials: N
authors.lastname: Regamey
authors.forename: Sarah
authors.initials: S
authors.lastname: Brown
authors.forename: Andrew
authors.initials: A
authors.lastname: Bush
authors.forename: Clare M
authors.initials: CM
authors.lastname: Lloyd
authors.forename: Jane C
authors.initials: JC
authors.lastname: Davies
mesh_terms: D001706:Biopsy; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D007223:Infant; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D058504:Th17 Cells / Q000276:immunology*