title: 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.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Case Western Reserve University, United States.
authors.forename: Patricia R
authors.initials: PR
authors.lastname: Taylor
authors.affiliation: Department of Pediatrics, Rainbow Babies and Children's Hospital, Case Western Reserve University, United States.
authors.forename: Tracey L
authors.initials: TL
authors.lastname: Bonfield
authors.affiliation: Department of Pediatrics, Rainbow Babies and Children's Hospital, Case Western Reserve University, United States.
authors.forename: James F
authors.initials: JF
authors.lastname: Chmiel
authors.affiliation: Department of Ophthalmology and Visual Sciences, Case Western Reserve University, United States; The University of California, Irvine, United States. Electronic address: Eric.Pearlman@uci.edu.
authors.forename: Eric
authors.initials: E
authors.lastname: Pearlman
mesh_terms: D000328:Adult; D000818:Animals; D003550:Cystic Fibrosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D053759:Interleukin-23 / Q000276:immunology* / Q000378:metabolism; D019272:Leukocyte Elastase / Q000276:immunology / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000276:immunology / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D011552:Pseudomonas Infections / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000276:immunology / Q000502:physiology; D053722:Receptors, Interleukin-17 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013183:Sputum / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: C508717:IL17A protein, human; D020381:Interleukin-17; D053759:Interleukin-23; D053722:Receptors, Interleukin-17; C093349:cystic fibrosis transmembrane conductance regulator delta F508; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D019272:Leukocyte Elastase; D020780:Matrix Metalloproteinase 9
keywords: CFTR; Cystic fibrosis; Elastase; F508del; F508del mice; IL-17A; IL-17A receptor; IL-17RC; MMP9; Neutrophil; Pseudomonas aeruginosa