Rationale Cystic fibrosis (CF) is characterized by bronchoalveolar neutrophilia, but submucosal lymphocytosis. We hypothesized that Th17 lymphocytes are part of this submucosal infiltrate.

Objectives 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 controls (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.

Measurements and main results IL-17+ cell counts (median[interquartile range]cells/mm(2)) were significantly higher in established CF (205[115-551]) and non-CF bronchiectasis (245[183-436]) than controls (53[12-82]) (p<0.01 for both). Newly diagnosed CF patients had intermediate counts (171[91-252]). IL-17 positive CD4+ T cells, γδT-cells, NKT 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 patients and controls (1.7[1.7-1.74]; 1.7[1.7-3]) and intermediate in non-CF bronchiectasis (9.1[1.7-34]pg/ml) (KW 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 NKT cells.