哮喘-慢性阻塞性肺疾病重叠和嗜酸性粒细胞慢性阻塞性肺疾病中嗜酸性粒细胞的炎症特征：一项多组学研究
2024/11/29
摘要
背景：伴有或不伴有哮喘的慢性阻塞性肺疾病（COPD）患者血液中嗜酸性粒细胞水平升高与病情加重和吸入皮质类固醇治疗效果有关。本研究旨在阐明哮喘-慢性阻塞性肺疾病重叠（ACO）和嗜酸性粒细胞慢性阻塞性肺疾病（eCOPD）患者嗜酸性粒细胞的炎症细胞特性。
方法 ：从健康志愿者、非eCOPD患者和ACO/eCOPD患者的外周血中分离嗜酸性粒细胞。进行了包括转录组学、蛋白质组学和脂质组学在内的多组学分析，然后进行了生物信息学数据分析。使用健康志愿者的嗜酸性粒细胞进行了体外实验，以研究嗜酸性粒细胞细胞变化的分子机制。
结果 ：蛋白质组学和转录组学分析表明，慢性阻塞性肺病患者的细胞特征主要表现为病毒感染（固醇调节元件结合蛋白-1表达升高）和炎症反应（IL1受体样1、Fc epsilon受体Ig和跨膜蛋白176B水平升高）。胆固醇代谢酶被确定为 ACO/eCOPD 相关因子。基因本体和通路富集分析表明了抗病毒反应、胆固醇代谢和炎症分子相关信号通路在 ACO/eCOPD 中的关键作用。脂质组学显示，在ACO/eCOPD中，环氧化酶衍生介质（包括前列腺素E2(PGE2)）的合成受损。体外评估证实，在ACO/eCOPD中，IL-33或TNF-α刺激与IL-5和IFN-γ刺激结合可诱导嗜酸性粒细胞的细胞特征。阿托伐他汀、地塞米松和PGE2对这些炎症变化有不同的调节作用。
结论：ACO/eCOPD与病毒感染和炎症环境有关。建议采用他汀类药物和吸入皮质类固醇的治疗策略来控制这些致病变化。
Inflammatory profile of eosinophils in asthma-COPD overlap and eosinophilic COPD: a multi-omics study
K. Sunata, J. Miyata, Y. Kawashima, R. Konno, M. Ishikawa, Y. Hasegawa, et al.
Abstract
BACKGRUND:Elevated blood eosinophil levels in patients with chronic obstructive pulmonary disease (COPD) with or without asthma are linked to increased exacerbations and the effectiveness of inhaled corticosteroid treatment. This study aimed to delineate the inflammatory cellular properties of eosinophils in patients with asthma-COPD overlap (ACO) and eosinophilic COPD (eCOPD).
METHODS: Eosinophils were isolated from the peripheral blood of healthy volunteers, patients with non-eCOPD, and those with ACO/eCOPD. Multi-omics analysis involving transcriptomics, proteomics, and lipidomics was performed, followed by bioinformatic data analyses. In vitro experiments using eosinophils from healthy volunteers were conducted to investigate the molecular mechanisms underlying cellular alterations in eosinophils.
RESULTS:Proteomics and transcriptomics analyses revealed cellular characteristics in overall COPD patients represented by viral infection (elevated expression of sterol regulatory element-binding protein-1) and inflammatory responses (elevated levels of IL1 receptor-like 1, Fc epsilon receptor Ig, and transmembrane protein 176B). Cholesterol metabolism enzymes were identified as ACO/eCOPD-related factors. Gene Ontology and pathway enrichment analyses demonstrated the key roles of antiviral responses, cholesterol metabolism, and inflammatory molecules-related signaling pathways in ACO/eCOPD. Lipidomics showed the impaired synthesis of cyclooxygenase-derived mediators including prostaglandin E2 (PGE2) in ACO/eCOPD. In vitro assessment confirmed that IL-33 or TNF-α stimulation combined with IL-5 and IFN-γ stimulation induced cellular signatures in eosinophils in ACO/eCOPD. Atorvastatin, dexamethasone, and PGE2 differentially modulated these inflammatory changes.
CONCLUSIONS:ACO/eCOPD is associated with viral infection and an inflammatory milieu. Therapeutic strategies using statins and inhaled corticosteroids are recommended to control these pathogenic changes.
背景：伴有或不伴有哮喘的慢性阻塞性肺疾病（COPD）患者血液中嗜酸性粒细胞水平升高与病情加重和吸入皮质类固醇治疗效果有关。本研究旨在阐明哮喘-慢性阻塞性肺疾病重叠（ACO）和嗜酸性粒细胞慢性阻塞性肺疾病（eCOPD）患者嗜酸性粒细胞的炎症细胞特性。
方法 ：从健康志愿者、非eCOPD患者和ACO/eCOPD患者的外周血中分离嗜酸性粒细胞。进行了包括转录组学、蛋白质组学和脂质组学在内的多组学分析，然后进行了生物信息学数据分析。使用健康志愿者的嗜酸性粒细胞进行了体外实验，以研究嗜酸性粒细胞细胞变化的分子机制。
结果 ：蛋白质组学和转录组学分析表明，慢性阻塞性肺病患者的细胞特征主要表现为病毒感染（固醇调节元件结合蛋白-1表达升高）和炎症反应（IL1受体样1、Fc epsilon受体Ig和跨膜蛋白176B水平升高）。胆固醇代谢酶被确定为 ACO/eCOPD 相关因子。基因本体和通路富集分析表明了抗病毒反应、胆固醇代谢和炎症分子相关信号通路在 ACO/eCOPD 中的关键作用。脂质组学显示，在ACO/eCOPD中，环氧化酶衍生介质（包括前列腺素E2(PGE2)）的合成受损。体外评估证实，在ACO/eCOPD中，IL-33或TNF-α刺激与IL-5和IFN-γ刺激结合可诱导嗜酸性粒细胞的细胞特征。阿托伐他汀、地塞米松和PGE2对这些炎症变化有不同的调节作用。
结论：ACO/eCOPD与病毒感染和炎症环境有关。建议采用他汀类药物和吸入皮质类固醇的治疗策略来控制这些致病变化。
（中日友好医院呼吸与危重症医学科 李春晓 摘译 林江涛 审校）
（Frontiers in Immunology 2024 Vol. 15 DOI: ARTN 144576910.3389/fimmu.2024.1445769）
（Frontiers in Immunology 2024 Vol. 15 DOI: ARTN 144576910.3389/fimmu.2024.1445769）
Inflammatory profile of eosinophils in asthma-COPD overlap and eosinophilic COPD: a multi-omics study
K. Sunata, J. Miyata, Y. Kawashima, R. Konno, M. Ishikawa, Y. Hasegawa, et al.
Abstract
BACKGRUND:Elevated blood eosinophil levels in patients with chronic obstructive pulmonary disease (COPD) with or without asthma are linked to increased exacerbations and the effectiveness of inhaled corticosteroid treatment. This study aimed to delineate the inflammatory cellular properties of eosinophils in patients with asthma-COPD overlap (ACO) and eosinophilic COPD (eCOPD).
METHODS: Eosinophils were isolated from the peripheral blood of healthy volunteers, patients with non-eCOPD, and those with ACO/eCOPD. Multi-omics analysis involving transcriptomics, proteomics, and lipidomics was performed, followed by bioinformatic data analyses. In vitro experiments using eosinophils from healthy volunteers were conducted to investigate the molecular mechanisms underlying cellular alterations in eosinophils.
RESULTS:Proteomics and transcriptomics analyses revealed cellular characteristics in overall COPD patients represented by viral infection (elevated expression of sterol regulatory element-binding protein-1) and inflammatory responses (elevated levels of IL1 receptor-like 1, Fc epsilon receptor Ig, and transmembrane protein 176B). Cholesterol metabolism enzymes were identified as ACO/eCOPD-related factors. Gene Ontology and pathway enrichment analyses demonstrated the key roles of antiviral responses, cholesterol metabolism, and inflammatory molecules-related signaling pathways in ACO/eCOPD. Lipidomics showed the impaired synthesis of cyclooxygenase-derived mediators including prostaglandin E2 (PGE2) in ACO/eCOPD. In vitro assessment confirmed that IL-33 or TNF-α stimulation combined with IL-5 and IFN-γ stimulation induced cellular signatures in eosinophils in ACO/eCOPD. Atorvastatin, dexamethasone, and PGE2 differentially modulated these inflammatory changes.
CONCLUSIONS:ACO/eCOPD is associated with viral infection and an inflammatory milieu. Therapeutic strategies using statins and inhaled corticosteroids are recommended to control these pathogenic changes.
