Airway IL-1β is related to disease severity and mucociliary function in bronchiectasis

TY - JOUR

T1 - Airway IL-1β is related to disease severity and mucociliary function in bronchiectasis

AU - Perea, Lidia

AU - Bottier, Mathieu

AU - Cant, Erin

AU - Richardson, Hollian

AU - Dicker, Alison J.

AU - Shuttleworth, Morven

AU - Giam, Yan Hui

AU - Abo-Leyah, Hani

AU - Finch, Simon

AU - Huang, Jeffrey T-J

AU - Shteinberg, Michal

AU - Goeminne, Pieter C

AU - Polverino, Eva

AU - Altenburg, Josje

AU - Blasi, Francesco

AU - Welte, Tobias

AU - Aliberti, Stefano

AU - Sibila, Oriol

AU - Chalmers, James D.

AU - Shoemark, Amelia

N1 - Copyright: ©The authors 2024. For reproduction rights and permissions contact [email protected]

PY - 2024/8

Y1 - 2024/8

N2 - Rationale The inflammasome is a key regulatory complex of the inflammatory response leading to interleukin-1β (IL-1β) release and activation. IL-1β amplifies inflammatory responses and induces mucus secretion and hyperconcentration in other diseases. The role of IL-1β in bronchiectasis has not been investigated. Objectives To characterise the role of airway IL-1β in bronchiectasis, including the association with mucus properties, ciliary function, airway inflammation, microbiome and disease severity. Methods Stable bronchiectasis patients were enrolled in an international cohort study (n=269). IL-1β was measured in sputum supernatant. A validation cohort also had sputum rheology and hydration measured (n=53). For analysis, patients were stratified according to the median value of IL-1β in the population (high versus low) to compare disease severity, airway infection, microbiome (16S rRNA sequencing), inflammation and caspase-1 activity. Primary human nasal epithelial cells grown in air–liquid interface culture were used to study the effect of IL-1β on cilia function. Results Patients with high sputum IL-1β had more severe disease, increased caspase-1 activity and an increased T-helper type 1, T-helper type 2 and neutrophil inflammatory response compared with patients with low IL-1β. The active-dominant form of IL-1β was associated with increased disease severity. High IL-1β was related to higher relative abundance of Proteobacteria in the microbiome and increased mucus solid content and viscoelastic properties. Chronic IL-1β treatment reduced the functionality of cilia and tight junctions of epithelial cells in vitro. Conclusions A subset of stable bronchiectasis patients show increased airway IL-1β, suggesting pulmonary inflammasome activation is linked with more severe disease, airway infection, mucus dehydration and epithelial dysfunction.

AB - Rationale The inflammasome is a key regulatory complex of the inflammatory response leading to interleukin-1β (IL-1β) release and activation. IL-1β amplifies inflammatory responses and induces mucus secretion and hyperconcentration in other diseases. The role of IL-1β in bronchiectasis has not been investigated. Objectives To characterise the role of airway IL-1β in bronchiectasis, including the association with mucus properties, ciliary function, airway inflammation, microbiome and disease severity. Methods Stable bronchiectasis patients were enrolled in an international cohort study (n=269). IL-1β was measured in sputum supernatant. A validation cohort also had sputum rheology and hydration measured (n=53). For analysis, patients were stratified according to the median value of IL-1β in the population (high versus low) to compare disease severity, airway infection, microbiome (16S rRNA sequencing), inflammation and caspase-1 activity. Primary human nasal epithelial cells grown in air–liquid interface culture were used to study the effect of IL-1β on cilia function. Results Patients with high sputum IL-1β had more severe disease, increased caspase-1 activity and an increased T-helper type 1, T-helper type 2 and neutrophil inflammatory response compared with patients with low IL-1β. The active-dominant form of IL-1β was associated with increased disease severity. High IL-1β was related to higher relative abundance of Proteobacteria in the microbiome and increased mucus solid content and viscoelastic properties. Chronic IL-1β treatment reduced the functionality of cilia and tight junctions of epithelial cells in vitro. Conclusions A subset of stable bronchiectasis patients show increased airway IL-1β, suggesting pulmonary inflammasome activation is linked with more severe disease, airway infection, mucus dehydration and epithelial dysfunction.

U2 - 10.1183/13993003.01966-2023

DO - 10.1183/13993003.01966-2023

M3 - Article

C2 - 38811046

AN - SCOPUS:85201438042

SN - 0903-1936

VL - 64

JO - European Respiratory Journal

JF - European Respiratory Journal

IS - 2

M1 - 2301966

ER -