鼻病毒诱发哮喘急性加重时的肺固有淋巴细胞反应：一项临床试验
2021/09/24
摘要
原理：2型固有淋巴细胞（ILC2s）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在病毒诱导的哮喘恶化中的作用尚不明确。
目的：研究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鼻病毒-16，并在接种后第3天和第8天接受支气管镜检查。使用流式细胞术在支气管肺泡灌洗（BAL）中定量测定肺ILC1s和ILC2s。评估BAL 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。
测量和主要结果：在基线时，哮喘患者的ILC2s显着高于健康受试者。在第8天，两组的ILC2s均从基线显著增加，哮喘显著高于健康受试者（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）具有显著更高的ILC2:ILC1比率。哮喘患者ILC2:ILC1比值增加与临床急性加重严重程度和鼻粘膜衬里液中2型细胞因子相关。
结论：与健康受试者相比，哮喘中ILC2占优势的炎症特征与鼻病毒感染的严重程度和持续时间增加相关，ILC2在病毒诱导的哮喘恶化发病机理中具有潜在作用。
Pulmonary Innate Lymphoid Cell Responses during Rhinovirus-induced Asthma Exacerbations In Vivo: A Clinical Trial
Jaideep Dhariwal, Aoife Cameron, Ernie Wong, Malte Paulsen, Belen Trujillo-Torralbo, Ajerico Del Rosario, Eteri Bakhsoliani, Tatiana Kebadze, Mark Almond, Hugo Farne, Leila Gogsadze, Julia Aniscenko, Batika Rana, Trevor T Hansel, David J Jackson, Onn Min Kon, Michael R Edwards, Roberto Solari, David Cousins, Ross P Walton, Sebastian L Johnston, MRC-GSK Strategic Alliance Consortium
Abstract
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, day 3 and day 8 post-inoculation. Pulmonary ILC1s and ILC2s were quantified in bronchoalveolar lavage (BAL) using flow cytometry. The ratio of BAL 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 healthy subjects. At day 8, ILC2s significantly increased from baseline in both groups, which was significantly higher in 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 asthma correlated with clinical exacerbation severity and type 2 cytokines in nasal mucosal lining fluid.
Conclusions：An ILC2-predominant inflammatory profile in 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.
原理：2型固有淋巴细胞（ILC2s）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在病毒诱导的哮喘恶化中的作用尚不明确。
目的：研究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鼻病毒-16，并在接种后第3天和第8天接受支气管镜检查。使用流式细胞术在支气管肺泡灌洗（BAL）中定量测定肺ILC1s和ILC2s。评估BAL 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。
测量和主要结果：在基线时，哮喘患者的ILC2s显着高于健康受试者。在第8天，两组的ILC2s均从基线显著增加，哮喘显著高于健康受试者（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）具有显著更高的ILC2:ILC1比率。哮喘患者ILC2:ILC1比值增加与临床急性加重严重程度和鼻粘膜衬里液中2型细胞因子相关。
结论：与健康受试者相比，哮喘中ILC2占优势的炎症特征与鼻病毒感染的严重程度和持续时间增加相关，ILC2在病毒诱导的哮喘恶化发病机理中具有潜在作用。
(中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校)
(Am J Respir Crit Care Med. 2021 Sep 1. doi: 10.1164/rccm.202010-3754OC.)
(Am J Respir Crit Care Med. 2021 Sep 1. doi: 10.1164/rccm.202010-3754OC.)
Pulmonary Innate Lymphoid Cell Responses during Rhinovirus-induced Asthma Exacerbations In Vivo: A Clinical Trial
Jaideep Dhariwal, Aoife Cameron, Ernie Wong, Malte Paulsen, Belen Trujillo-Torralbo, Ajerico Del Rosario, Eteri Bakhsoliani, Tatiana Kebadze, Mark Almond, Hugo Farne, Leila Gogsadze, Julia Aniscenko, Batika Rana, Trevor T Hansel, David J Jackson, Onn Min Kon, Michael R Edwards, Roberto Solari, David Cousins, Ross P Walton, Sebastian L Johnston, MRC-GSK Strategic Alliance Consortium
Abstract
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, day 3 and day 8 post-inoculation. Pulmonary ILC1s and ILC2s were quantified in bronchoalveolar lavage (BAL) using flow cytometry. The ratio of BAL 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 healthy subjects. At day 8, ILC2s significantly increased from baseline in both groups, which was significantly higher in 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 asthma correlated with clinical exacerbation severity and type 2 cytokines in nasal mucosal lining fluid.
Conclusions：An ILC2-predominant inflammatory profile in 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.
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呼出气一氧化氮与哮喘和常年性致敏相关的上呼吸道炎症性疾病相关性的横断面研究
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TL1A/DR3轴在嗜酸性粒细胞性哮喘患者ILC2s活化中的作用
