Developmental immune network of airway lymphocytes and innate immune cells in patients with stable COPD
IntroductionChronic obstructive pulmonary disease (COPD) is characterized by persistent airway inflammation and immune dysfunction. However, the molecular alterations and precise origins of immune cells in COPD airways remain poorly understood.MethodsHere, CD45+ immune cells in bronchoalveolar lavag...
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Frontiers Media S.A.
2025-06-01
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| author | Lanlan Liu Mei Zhou Shengwen Sun Long Chen Dehu Li Dehu Li Jiaxi Lv Rui Cheng Rui Cheng Jianchu Zhang Jianghua Wu Jianghua Wu Xianzhi Xiong |
| author_facet | Lanlan Liu Mei Zhou Shengwen Sun Long Chen Dehu Li Dehu Li Jiaxi Lv Rui Cheng Rui Cheng Jianchu Zhang Jianghua Wu Jianghua Wu Xianzhi Xiong |
| author_sort | Lanlan Liu |
| collection | DOAJ |
| description | IntroductionChronic obstructive pulmonary disease (COPD) is characterized by persistent airway inflammation and immune dysfunction. However, the molecular alterations and precise origins of immune cells in COPD airways remain poorly understood.MethodsHere, CD45+ immune cells in bronchoalveolar lavage fluid and peripheral blood mononuclear cells were collected from four COPD patients and four healthy smokers to provide a comprehensive single-cell transcriptomic atlas of immune cells in COPD airways.ResultsNotably, CD8+ T cells exhibited increased exhaustion, reduced cytotoxicity, and decreased TCR diversity in COPD airways. Especially, we identified two distinct exhausted CD8+ T cell clusters (CD8Tex_PDCD1 and CD8Trm_LAG3) originating from different developmental trajectories. Regulatory T cells had a reduced proportion and regulatory capacity in COPD airways, while CD4+ tissue-resident memory T cells displayed excessive Th2 responses and diminished Th1 responses. Additionally, monocyte-derived alveolar macrophages (Macro_SPP1) underwent lipid metabolic reprogramming and exhibited a shift to an anti-inflammatory phenotype with reduced phagocytosis and protease-antiprotease imbalance in COPD airways. Furthermore, macrophages (particularly Macro_SPP1) showed increased interactions with T cells via SPP1 and GALECTIN signaling, likely contributing to T cell suppression in COPD airways.ConclusionTogether, these findings elucidate the dysregulated immune responses in COPD airways and provide a valuable resource for identifying potential therapeutic targets to restore immune homeostasis in COPD. |
| format | Article |
| id | doaj-art-0d89a699370e4d89a73e6b5f024c680d |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-0d89a699370e4d89a73e6b5f024c680d2025-08-20T02:07:41ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-06-011610.3389/fimmu.2025.16146551614655Developmental immune network of airway lymphocytes and innate immune cells in patients with stable COPDLanlan Liu0Mei Zhou1Shengwen Sun2Long Chen3Dehu Li4Dehu Li5Jiaxi Lv6Rui Cheng7Rui Cheng8Jianchu Zhang9Jianghua Wu10Jianghua Wu11Xianzhi Xiong12Department of Respiratory and Critical Care Medicine, Hubei Province Clinical Research Center for Major Respiratory Diseases, Key Laboratory of Pulmonary Diseases of National Health Commission, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Respiratory and Critical Care Medicine, Hubei Province Clinical Research Center for Major Respiratory Diseases, Key Laboratory of Pulmonary Diseases of National Health Commission, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Respiratory and Critical Care Medicine, Hubei Province Clinical Research Center for Major Respiratory Diseases, Key Laboratory of Pulmonary Diseases of National Health Commission, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Respiratory and Critical Care Medicine, Hubei Province Clinical Research Center for Major Respiratory Diseases, Key Laboratory of Pulmonary Diseases of National Health Commission, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Respiratory and Critical Care Medicine, Hubei Province Clinical Research Center for Major Respiratory Diseases, Key Laboratory of Pulmonary Diseases of National Health Commission, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaUndergraduate Research Interest Group, Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaBiological Sciences Class 2302, College of Life Sciences and Technology, Huazhong Agricultural University, Wuhan, ChinaDepartment of Respiratory and Critical Care Medicine, Hubei Province Clinical Research Center for Major Respiratory Diseases, Key Laboratory of Pulmonary Diseases of National Health Commission, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Respiratory and Critical Care Medicine, Hubei Province Clinical Research Center for Major Respiratory Diseases, Key Laboratory of Pulmonary Diseases of National Health Commission, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Medical Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, ChinaDepartment of Respiratory and Critical Care Medicine, Hubei Province Clinical Research Center for Major Respiratory Diseases, Key Laboratory of Pulmonary Diseases of National Health Commission, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaIntroductionChronic obstructive pulmonary disease (COPD) is characterized by persistent airway inflammation and immune dysfunction. However, the molecular alterations and precise origins of immune cells in COPD airways remain poorly understood.MethodsHere, CD45+ immune cells in bronchoalveolar lavage fluid and peripheral blood mononuclear cells were collected from four COPD patients and four healthy smokers to provide a comprehensive single-cell transcriptomic atlas of immune cells in COPD airways.ResultsNotably, CD8+ T cells exhibited increased exhaustion, reduced cytotoxicity, and decreased TCR diversity in COPD airways. Especially, we identified two distinct exhausted CD8+ T cell clusters (CD8Tex_PDCD1 and CD8Trm_LAG3) originating from different developmental trajectories. Regulatory T cells had a reduced proportion and regulatory capacity in COPD airways, while CD4+ tissue-resident memory T cells displayed excessive Th2 responses and diminished Th1 responses. Additionally, monocyte-derived alveolar macrophages (Macro_SPP1) underwent lipid metabolic reprogramming and exhibited a shift to an anti-inflammatory phenotype with reduced phagocytosis and protease-antiprotease imbalance in COPD airways. Furthermore, macrophages (particularly Macro_SPP1) showed increased interactions with T cells via SPP1 and GALECTIN signaling, likely contributing to T cell suppression in COPD airways.ConclusionTogether, these findings elucidate the dysregulated immune responses in COPD airways and provide a valuable resource for identifying potential therapeutic targets to restore immune homeostasis in COPD.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1614655/fullchronic obstructive pulmonary diseasesingle-cell RNA sequencingT cell exhaustionalveolar macrophageslipid metabolic reprogramming |
| spellingShingle | Lanlan Liu Mei Zhou Shengwen Sun Long Chen Dehu Li Dehu Li Jiaxi Lv Rui Cheng Rui Cheng Jianchu Zhang Jianghua Wu Jianghua Wu Xianzhi Xiong Developmental immune network of airway lymphocytes and innate immune cells in patients with stable COPD Frontiers in Immunology chronic obstructive pulmonary disease single-cell RNA sequencing T cell exhaustion alveolar macrophages lipid metabolic reprogramming |
| title | Developmental immune network of airway lymphocytes and innate immune cells in patients with stable COPD |
| title_full | Developmental immune network of airway lymphocytes and innate immune cells in patients with stable COPD |
| title_fullStr | Developmental immune network of airway lymphocytes and innate immune cells in patients with stable COPD |
| title_full_unstemmed | Developmental immune network of airway lymphocytes and innate immune cells in patients with stable COPD |
| title_short | Developmental immune network of airway lymphocytes and innate immune cells in patients with stable COPD |
| title_sort | developmental immune network of airway lymphocytes and innate immune cells in patients with stable copd |
| topic | chronic obstructive pulmonary disease single-cell RNA sequencing T cell exhaustion alveolar macrophages lipid metabolic reprogramming |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1614655/full |
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