{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T19:57:46Z","timestamp":1791835066823,"version":"4.3.4"},"reference-count":114,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T00:00:00Z","timestamp":1750032000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Chronic 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here, 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Notably, 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Together, 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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1614655","type":"journal-article","created":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T04:10:36Z","timestamp":1750047036000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Developmental immune network of airway lymphocytes and innate immune cells in patients with stable COPD"],"prefix":"10.3389","volume":"16","author":[{"given":"Lanlan","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengwen","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dehu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxi","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianchu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianghua","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianzhi","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202301-0106PP","article-title":"Global initiative for chronic obstructive lung disease 2023 report: gold executive summary","volume":"207","author":"Agust\u00ed","year":"2023","journal-title":"Am J Respir Crit Care Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(17)31222-9","article-title":"Chronic obstructive pulmonary disease","volume":"389","author":"Rabe","year":"2017","journal-title":"Lancet (London England)"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(22)00470-6","article-title":"Chronic obstructive pulmonary disease","volume":"399","author":"Christenson","year":"2022","journal-title":"Lancet (London England)"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2006.062802","article-title":"Developing copd: A 25 year follow up study of the general population","volume":"61","author":"L\u00f8kke","year":"2006","journal-title":"Thorax"},{"key":"B5","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1165\/rcmb.2022-0131OC","article-title":"Chronic obstructive pulmonary disease and cigarette smoke lead to dysregulated mucosal-associated invariant T-cell activation","volume":"68","author":"Huber","year":"2023","journal-title":"Am J Respir Cell Mol Biol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201504-0782OC","article-title":"Dysregulation of antiviral function of Cd8(+) T cells in the chronic obstructive pulmonary disease lung. 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