识别与哮喘2型嗜酸性炎症相关的支气管上皮基因
2025/06/16
摘要
背景：气道炎症在哮喘的发病机制和病理生理过程中起关键作用，然而介导气道炎症的分子通路尚未完全明确，尤其是以嗜酸性粒细胞增多和呼出气一氧化氮（FeNO）水平升高为特征的2型（T2）炎症。
目的：本研究旨在筛选上皮细胞刷检样本中表达水平与支气管肺泡灌洗液（BAL）中嗜酸性粒细胞增多及FeNO水平均相关的基因。
方法：作者对过敏性哮喘患者进行了节段性过敏原支气管激发试验，并于激发前及激发后48小时采集BAL中的细胞和刷检样本进行RNA测序分析，以揭示嗜酸性粒细胞募集及FeNO水平变化的调控机制。
结果：过敏原支气管激发试验可显著升高FeNO水平，且FeNO水平与嗜酸性粒细胞增多程度呈正相关。研究从刷检样本中鉴定出13个基因，其表达水平在支气管激发试验后发生显著改变，并与气道嗜酸性粒细胞增多及FeNO水平均相关。其中上皮细胞产物CDH26/钙黏蛋白-26通过促进2型炎症反应（表现为嗜酸性粒细胞增多和FeNO升高）发挥作用，这一机制经BAL中促2型炎症因子和促嗜酸性粒细胞因子介导的因果中介分析得以验证。在抑制嗜酸性粒细胞增多和降低FeNO的相关基因中，HEY2被证实能够增强细胞增殖、迁移、侵袭和上皮-间质转化能力，同时抑制细胞凋亡。
结论：本项基于过敏性哮喘患者的全转录组测序分析表明，多个上皮细胞基因（尤其是CDH26）可能在哮喘2型炎症的启动或增强过程中发挥关键作用。
关键词： 哮喘；过敏原激发；支气管刷检；支气管肺泡灌洗；嗜酸性粒细胞；一氧化氮；变态反应；RNA测序；多重蛋白检测；CDH26；2型免疫反应
文献来源：（Esnault S, Dill-McFarland K A, Altman M C, et al. Identification of bronchial epithelial genes associated with type 2 eosinophilic inflammation in asthma[J]. Journal of Allergy and Clinical Immunology, 2025, 155(5): 1510-1520. DOI: 10.1016/j.jaci.2024.12.1089.）
背景：气道炎症在哮喘的发病机制和病理生理过程中起关键作用，然而介导气道炎症的分子通路尚未完全明确，尤其是以嗜酸性粒细胞增多和呼出气一氧化氮（FeNO）水平升高为特征的2型（T2）炎症。
目的：本研究旨在筛选上皮细胞刷检样本中表达水平与支气管肺泡灌洗液（BAL）中嗜酸性粒细胞增多及FeNO水平均相关的基因。
方法：作者对过敏性哮喘患者进行了节段性过敏原支气管激发试验，并于激发前及激发后48小时采集BAL中的细胞和刷检样本进行RNA测序分析，以揭示嗜酸性粒细胞募集及FeNO水平变化的调控机制。
结果：过敏原支气管激发试验可显著升高FeNO水平，且FeNO水平与嗜酸性粒细胞增多程度呈正相关。研究从刷检样本中鉴定出13个基因，其表达水平在支气管激发试验后发生显著改变，并与气道嗜酸性粒细胞增多及FeNO水平均相关。其中上皮细胞产物CDH26/钙黏蛋白-26通过促进2型炎症反应（表现为嗜酸性粒细胞增多和FeNO升高）发挥作用，这一机制经BAL中促2型炎症因子和促嗜酸性粒细胞因子介导的因果中介分析得以验证。在抑制嗜酸性粒细胞增多和降低FeNO的相关基因中，HEY2被证实能够增强细胞增殖、迁移、侵袭和上皮-间质转化能力，同时抑制细胞凋亡。
结论：本项基于过敏性哮喘患者的全转录组测序分析表明，多个上皮细胞基因（尤其是CDH26）可能在哮喘2型炎症的启动或增强过程中发挥关键作用。
关键词： 哮喘；过敏原激发；支气管刷检；支气管肺泡灌洗；嗜酸性粒细胞；一氧化氮；变态反应；RNA测序；多重蛋白检测；CDH26；2型免疫反应
文献来源：（Esnault S, Dill-McFarland K A, Altman M C, et al. Identification of bronchial epithelial genes associated with type 2 eosinophilic inflammation in asthma[J]. Journal of Allergy and Clinical Immunology, 2025, 155(5): 1510-1520. DOI: 10.1016/j.jaci.2024.12.1089.）
（南方医科大学南方医院 黄海伦 龚钊乾 赵文驱）
Abstract
Background：Airway inflammation plays a critical role in asthma pathogenesis and pathophysiology, but the molecular pathways contributing to airway inflammation are not fully known, particularly type 2 (T2) inflammation characterized by both eosinophilia and higher fractional exhaled nitric oxide (Feno) levels.
Objective：We sought to identify genes whose level of expression in epithelial brushing samples were associated with both bronchoalveolar lavage (BAL) eosinophilia and generation of Feno.
Methods：We performed segmental allergen bronchoprovocation (SBP-Ag) in participants with asthma, then RNA sequencing analyses of BAL cells and brushing samples before and 48 hours after SBP-Ag to identify regulation of eosinophil recruitment and Feno changes.
Results：Allergen bronchoprovocation increased Feno levels, which correlated with eosinophilia. Thirteen genes were identified in brushing samples, whose expression changed in response to SBP-Ag and correlated with both airway eosinophilia and Feno levels after SBP-Ag. Among these 13 genes, epithelial cell product CDH26/cadherin-26 contributed to the amplification of T2 inflammation, as reflected by eosinophilia and Feno, and causal mediation analyses with pro-T2 and proeosinophilic cytokine mediators in BAL fluids. Among the genes associated with reduced eosinophilia and Feno, HEY2 is known to enhance cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition, as well as to reduce apoptosis.
Conclusion：This unbiased RNA sequencing analysis in participants with allergic asthma revealed several epithelial cell genes, particularly CDH26, that may be critical for the development or augmentation of T2 inflammation in asthma.
Key words：Asthma; allergic challenge; bronchial brushing; bronchoalveolar lavage; eosinophils nitric oxide; allergy; RNA sequencing; multiplex protein assay; CDH26; type 2 immune response
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哮喘与新冠肺炎：基于不同内表型揭示预后差异及治疗影响
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老年队列哮喘急性发作患者的共病模式及其预后影响
