Neutrophils from F508del cystic fibrosis patients produce IL-17A and express IL-23 - dependent IL-17RC

Abstract

Cystic fibrosis (CF) is a chronic pulmonary disease that is associated with persistent microbial infection and chronic neutrophil infiltration, and also with elevated production of the pro-inflammatory cytokine IL-17A (IL-17). In the current study, we examined IL-17 and the inducible IL-17RC receptor subunit in neutrophils from Pseudomonas aeruginosa infected F508del CF patients at the time of pulmonary exacerbation, and again following intravenous antibiotic treatment. Neutrophils expressed Il17a and Il17rc transcripts and protein at the time of pulmonary exacerbation, which were absent following antibiotic treatment. Further, CF sputum induced IL-23 - dependent Il17rc expression in neutrophils from healthy individuals. Similarly, IL-17 producing neutrophils were detected in F508del and Cftr(-/-) mice infected intranasally with P. aeruginosa. In the sputum of CF subjects, the percentage IL-17 producing neutrophils correlated with elastase and MMP9 activity; therefore, this population of neutrophils may be an important contributor to the severity of pulmonary disease in CF patients.

Keywords: CFTR; Cystic fibrosis; Elastase; F508del; F508del mice; IL-17A; IL-17A receptor; IL-17RC; MMP9; Neutrophil; Pseudomonas aeruginosa.