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Airway IL-1β is related to disease severity and mucociliary function in bronchiectasis
European Respiratory Journal ( IF 16.6 ) Pub Date : 2024-08-15 , DOI: 10.1183/13993003.01966-2023
Lidia Perea 1, 2 , Mathieu Bottier 1, 3 , Erin Cant 1 , Hollian Richardson 1 , Alison J Dicker 1 , Morven Shuttleworth 1 , Yan Hui Giam 1 , Hani Abo-Leyah 1 , Simon Finch 1 , Jeffrey T-J Huang 4 , Michal Shteinberg 5 , Pieter C Goeminne 6 , Eva Polverino 7 , Josje Altenburg 8 , Francesco Blasi 9, 10 , Tobias Welte 11 , Stefano Aliberti 12, 13 , Oriol Sibila 14 , James D Chalmers 1, 15 , Amelia Shoemark 15, 16
Affiliation  

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.



中文翻译:


气道 IL-1β 与支气管扩张症的疾病严重程度和粘膜纤毛功能相关


 基本原理


炎症小体是导致白介素 1β (IL-1β) 释放和激活的炎症反应的关键调节复合体。 IL-1β 在其他疾病中会放大炎症反应并诱导粘液分泌和过度浓缩。 IL-1β 在支气管扩张中的作用尚未被研究。

 目标


表征气道 IL-1β 在支气管扩张中的作用,包括与粘液特性、纤毛功能、气道炎症、微生物组和疾病严重程度的关联。

 方法


稳定型支气管扩张患者被纳入一项国际队列研究 (n=269)。测定痰上清液中的 IL-1β。验证队列还测量了痰流变学和水合作用(n = 53)。为了进行分析,根据人群中 IL-1β 的中值(高低)对患者进行分层,以比较疾病严重程度、气道感染、微生物组(16S rRNA 测序)、炎症和 caspase-1 活性。使用气液界面培养物中生长的原代人鼻上皮细胞来研究 IL-1β 对纤毛功能的影响。

 结果


与IL-1β低的患者相比,痰IL-1β高的患者病情更严重,caspase-1活性增加,1型辅助T、2型T辅助和中性粒细胞炎症反应增加。 IL-1β 的活性主导形式与疾病严重程度增加相关。高 IL-1β 与微生物组中变形菌相对丰度较高以及粘液固体含量和粘弹性特性增加有关。体外实验中,慢性IL-1β治疗会降低纤毛和上皮细胞紧密连接的功能。

 结论


一部分稳定型支气管扩张患者的气道 IL-1β 水平升高,表明肺部炎症小体激活与更严重的疾病、气道感染、粘液脱水和上皮功能障碍有关。

更新日期:2024-08-15
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