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Pulmonary Innate Lymphoid Cell Responses during Rhinovirus-induced Asthma Exacerbations In Vivo: A Clinical Trial.
American Journal of Respiratory and Critical Care Medicine ( IF 24.7 ) Pub Date : 2021-12-01 , DOI: 10.1164/rccm.202010-3754oc
Jaideep Dhariwal 1, 2, 3 , Aoife Cameron 1, 2 , Ernie Wong 1, 2 , Malte Paulsen 4 , Maria-Belen Trujillo-Torralbo 1, 2 , Ajerico Del Rosario 1, 2 , Eteri Bakhsoliani 1, 2 , Tatiana Kebadze 1, 2 , Mark Almond 1, 2 , Hugo Farne 1, 2 , Leila Gogsadze 1, 2 , Julia Aniscenko 1, 2 , Batika M J Rana 2, 5 , Trevor T Hansel 1, 2 , David J Jackson 2, 4, 5 , Onn Min Kon 1, 2 , Michael R Edwards 1, 2 , Roberto Solari 1, 2 , David J Cousins 2, 5, 6 , Ross P Walton 1, 2 , Sebastian L Johnston 1, 2 ,
Affiliation  

Rationale: Type 2 innate lymphoid cells (ILC2s) are significant sources of type 2 cytokines, which are implicated in the pathogenesis of asthma and asthma exacerbations. The role of ILC2s in virus-induced asthma exacerbations is not well characterized. Objectives: To characterize pulmonary ILC responses following experimental rhinovirus challenge in patients with moderate asthma and healthy subjects. Methods: Patients with moderate asthma and healthy subjects were inoculated with rhinovirus-16 and underwent bronchoscopy at baseline and at Day 3, and Day 8 after inoculation. Pulmonary ILC1s and ILC2s were quantified in bronchoalveolar lavage using flow cytometry. The ratio of bronchoalveolar lavage ILC2:ILC1 was assessed to determine their relative contributions to the clinical and immune response to rhinovirus challenge. Measurements and Main Results: At baseline, ILC2s were significantly higher in patients with asthma than in healthy subjects. At Day 8, ILC2s significantly increased from baseline in both groups, which was significantly higher in patients with asthma than in healthy subjects (all comparisons P < 0.05). In healthy subjects, ILC1s increased from baseline at Day 3 (P = 0.001), while in patients with asthma, ILC1s increased from baseline at Day 8 (P = 0.042). Patients with asthma had significantly higher ILC2:ILC1 ratios at baseline (P = 0.024) and Day 8 (P = 0.005). Increased ILC2:ILC1 ratio in patients with asthma correlated with clinical exacerbation severity and type 2 cytokines in nasal mucosal lining fluid. Conclusions: An ILC2-predominant inflammatory profile in patients with asthma was associated with increased severity and duration of rhinovirus infection compared with healthy subjects, supporting the potential role of ILC2s in the pathogenesis of virus-induced asthma exacerbations.

中文翻译:

鼻病毒诱导的体内哮喘恶化期间的肺先天淋巴细胞反应:临床试验。

基本原理:2 型先天性淋巴细胞 (ILC2) 是 2 型细胞因子的重要来源,与哮喘和哮喘恶化的发病机制有关。ILC2s 在病毒诱导的哮喘发作中的作用尚未得到很好的表征。目的:描述中度哮喘患者和健康受试者在实验性鼻病毒攻击后的肺 ILC 反应。方法:中度哮喘患者和健康受试者接种 rhinovirus-16 并在基线和接种后第 3 天和第 8 天进行支气管镜检查。使用流式细胞术在支气管肺泡灌洗液中定量肺 ILC1 和 ILC2。评估支气管肺泡灌洗液 ILC2:ILC1 的比率以确定它们对鼻病毒攻击的临床和免疫反应的相对贡献。测量结果和主要结果:在基线时,哮喘患者的 ILC2 显着高于健康受试者。在第 8 天,两组的 ILC2s 均较基线显着增加,哮喘患者显着高于健康受试者(所有比较 P < 0.05)。在健康受试者中,ILC1 在第 3 天从基线增加(P = 0.001),而在哮喘患者中,ILC1 在第 8 天从基线增加(P = 0.042)。哮喘患者在基线 (P = 0.024) 和第 8 天 (P = 0.005) 时的 ILC2:ILC1 比率显着升高。哮喘患者 ILC2:ILC1 比值增加与临床恶化严重程度和鼻粘膜衬液中的 2 型细胞因子相关。结论:
更新日期:2021-09-01
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