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慢性阻塞性肺疾病发病机制中T细胞介导的免疫信号网络动力学

Dynamics of T Cell-Mediated Immune Signaling Network During Pathogenesis of Chronic Obstructive Pulmonary Disease.

作者信息

Lee Chae Min, Kim Andrew Sehoon, Kim Minki, Jeong Jae Woong, Jo Sugyeong, Hwang Nahee, Fang Sungsoon

机构信息

Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Korea.

Department of Biomedical Sciences, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

出版信息

Yonsei Med J. 2025 Jun;66(6):354-365. doi: 10.3349/ymj.2024.0227.

DOI:10.3349/ymj.2024.0227
PMID:40414827
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12116870/
Abstract

PURPOSE

Chronic obstructive pulmonary disease (COPD) is characterized by alveolar destruction and increased inflammation, leading to respiratory symptoms. This study aimed to identify the traits for COPD progression from mild to severe stages. Additionally, we explored the correlation between coronavirus disease-2019 (COVID-19) and COPD to uncover overlapping respiratory patterns.

MATERIALS AND METHODS

Bulk RNA sequencing was conducted on data from 43 healthy individuals and 39 COPD patients across one dataset (GSE239897) to distinguish COPD characteristics. Single-cell RNA analysis was then performed on samples from seven mild patients, seven moderate patients, and three severe patients from three datasets (GSE167295, GSE173896, and GSE227691) to analyze disease progression. Finally, single-nuclei RNA analysis was applied to data from seven healthy individuals and 20 COVID-19 patients from one dataset (GSE171524) to compare the two conditions.

RESULTS

Bulk RNA sequencing revealed enhanced inflammatory pathways in COPD patients, indicating increased inflammation. Single-cell RNA sequencing showed a stronger inflammatory response from mild to moderate COPD with a decrease from moderate to severe stages. COVID-19 displayed similar biological patterns to moderate COPD, suggesting that stage-specific COPD analysis could enhance COVID-19 management.

CONCLUSION

The analysis found that immune responses increased from mild to moderate stages but declined in severe cases, marked by reduced pulmonary T cell activation. The overlap between moderate COPD and COVID-19 suggests shared therapeutic strategies, warranting further investigation.

摘要

目的

慢性阻塞性肺疾病(COPD)的特征是肺泡破坏和炎症增加,导致呼吸道症状。本研究旨在确定COPD从轻度到重度阶段进展的特征。此外,我们探讨了2019冠状病毒病(COVID-19)与COPD之间的相关性,以揭示重叠的呼吸模式。

材料和方法

对来自一个数据集(GSE239897)的43名健康个体和39名COPD患者的数据进行批量RNA测序,以区分COPD特征。然后对来自三个数据集(GSE167295、GSE173896和GSE227691)的7名轻度患者、7名中度患者和3名重度患者的样本进行单细胞RNA分析,以分析疾病进展。最后,将单核RNA分析应用于来自一个数据集(GSE171524)的7名健康个体和20名COVID-19患者的数据,以比较这两种情况。

结果

批量RNA测序显示COPD患者的炎症途径增强,表明炎症增加。单细胞RNA测序显示,从轻度到中度COPD炎症反应更强,从中度到重度阶段则下降。COVID-19表现出与中度COPD相似的生物学模式,表明特定阶段的COPD分析可以加强COVID-19的管理。

结论

分析发现,免疫反应从轻度到中度阶段增加,但在重度病例中下降,以肺T细胞激活减少为特征。中度COPD和COVID-19之间的重叠表明存在共同的治疗策略,值得进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc6f/12116870/49b1ca7df0b3/ymj-66-354-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc6f/12116870/793c91b917b1/ymj-66-354-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc6f/12116870/49b1ca7df0b3/ymj-66-354-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc6f/12116870/793c91b917b1/ymj-66-354-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc6f/12116870/1da381723cab/ymj-66-354-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc6f/12116870/2f9a25fdc3da/ymj-66-354-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc6f/12116870/7e0c7ac06fe0/ymj-66-354-g004.jpg
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本文引用的文献

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Am J Respir Crit Care Med. 2023 Dec 1;208(11):1177-1195. doi: 10.1164/rccm.202305-0924OC.
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The Complex Association between COPD and COVID-19.慢性阻塞性肺疾病(COPD)与2019冠状病毒病(COVID-19)之间的复杂关联。
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Heme oxygenase-1 determines the cell fate of ferroptotic death of alveolar macrophages in COPD.血红素加氧酶-1 决定 COPD 肺泡巨噬细胞铁死亡的细胞命运。
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Global Initiative for Chronic Obstructive Lung Disease 2023 Report: GOLD Executive Summary.全球慢性阻塞性肺疾病倡议 2023 年报告:GOLD 执行摘要。
Eur Respir J. 2023 Apr 1;61(4). doi: 10.1183/13993003.00239-2023. Print 2023 Apr.
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SARS-CoV-2 viral load and shedding kinetics.SARS-CoV-2 病毒载量和脱落动力学。
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Forthcoming complications in recovered COVID-19 patients with COPD and asthma; possible therapeutic opportunities.康复的 COVID-19 合并 COPD 和哮喘患者的即将出现的并发症;可能的治疗机会。
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