Adult Non-Cystic Fibrosis Bronchiectasis Is Characterised by Airway Luminal Th17 Pathway Activation

dc.contributor.author Chen, Alice
dc.contributor.author Martin, Megan L
dc.contributor.author Lourie, R
dc.contributor.author Rogers, Geraint B
dc.contributor.author Burr, Lucy D
dc.contributor.author Hasnain, Sumaira Z
dc.contributor.author Bowler, Simon D
dc.contributor.author McGuckin, Michael A
dc.contributor.author Serisier, D
dc.date.accessioned 2016-03-01T05:14:23Z
dc.date.available 2016-03-01T05:14:23Z
dc.date.issued 2015
dc.description Copyright © 2015 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. en
dc.description.abstract BACKGROUND: Non-cystic fibrosis (CF) bronchiectasis is characterised by chronic airway infection and neutrophilic inflammation, which we hypothesised would be associated with Th17 pathway activation. METHODS: Th17 pathway cytokines were quantified in bronchoalveolar lavage fluid (BALF), and gene expression of IL-17A, IL-1β, IL-8 and IL-23 determined from endobronchial biopsies (EBx) in 41 stable bronchiectasis subjects and 20 healthy controls. Relationships between IL-17A levels and infection status, important clinical measures and subsequent Pseudomonas aeruginosa infection were determined. RESULTS: BALF levels of all Th17 cytokines (median (IQR) pg/mL) were significantly higher in bronchiectasis than control subjects, including IL-17A (1.73 (1.19, 3.23) vs. 0.27 (0.24, 0.35), 95% CI 1.05 to 2.21, p<0.0001) and IL-23 (9.48 (4.79, 15.75) vs. 0.70 (0.43, 1.79), 95% CI 4.68 to 11.21, p<0.0001). However, BALF IL-17A levels were not associated with clinical measures or airway microbiology, nor predictive of subsequent P. aeruginosa infection. Furthermore, gene expression of IL-17A in bronchiectasis EBx did not differ from control. In contrast, gene expression (relative to medians of controls) in bronchiectasis EBx was significantly higher than control for IL1β (4.12 (1.24, 8.05) vs 1 (0.13, 2.95), 95% CI 0.05 to 4.07, p = 0.04) and IL-8 (3.75 (1.64, 11.27) vs 1 (0.54, 3.89), 95% CI 0.32 to 4.87, p = 0.02) and BALF IL-8 and IL-1α levels showed significant relationships with clinical measures and airway microbiology. P. aeruginosa infection was associated with increased levels of IL-8 while Haemophilus influenzae was associated with increased IL-1α. CONCLUSIONS AND CLINICAL RELEVANCE: Established adult non-CF bronchiectasis is characterised by luminal Th17 pathway activation, however this pathway may be relatively less important than activation of non-antigen-specific innate neutrophilic immunity. en
dc.identifier.citation Chen AC, Martin ML, Lourie R, Rogers GB, Burr LD, Hasnain SZ, Bowler SD, McGuckin MA, Serisier DJ. Adult non-cystic fibrosis bronchiectasis is characterised by airway luminal Th17 pathway activation. PLoS One. 2015 Mar 30;10(3):e0119325. doi: 10.1371/journal.pone.0119325. en
dc.identifier.doi https://doi.org/10.1371/journal.pone.0119325 en
dc.identifier.issn 1932-6203
dc.identifier.uri http://hdl.handle.net/2328/36000
dc.language.iso en
dc.publisher Public Library of Science en
dc.rights Copyright © 2015 Chen et al en
dc.rights.holder Chen et al en
dc.rights.license CC-BY
dc.title Adult Non-Cystic Fibrosis Bronchiectasis Is Characterised by Airway Luminal Th17 Pathway Activation en
dc.type Article en
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