Dysregulated NK cell activation and myeloid-lymphoid imbalance underpin COPD progression: insights from high-dimensional immune profiling and smoking-induced immune remodeling

作者：Qin Qiao, Yazheng Yang, Ke Huang, Hongtao Niu, Xiaoxia Ren, Shiwei Qumu, Wei Li, Chen Dong, Ting Yang, Ling Ni · 发表于：Frontiers in Immunology · 年份：2025 · DOI：10.3389/fimmu.2025.1623319 · 被引用次数：2 · 研究领域：Chronic Obstructive Pulmonary Disease (COPD) Research、Pediatric health and respiratory diseases、Immune Cell Function and Interaction

Background Chronic obstructive pulmonary disease (COPD) is a significant global health concern, marked by persistent inflammation and immune dysregulation. Although it is widespread and has substantial clinical implications, the systemic immune mechanisms driving disease progression are not fully understood. Since blood contains a diverse array of immune cells and offers a non-invasive means of assessing immune homeostasis and overall physiological status, investigating immune dysregulation through blood sampling offers considerable value for both basic research and clinical application. This approach can provide novel insights into the pathogenesis of COPD. Methods This study employed high-dimensional flow cytometry and RNA sequencing to comprehensively characterize peripheral immune cells from a cohort of 69 COPD patients spanning clinical stages 1 to 4, alongside 41 healthy donors as controls. To capture granulocyte populations typically excluded from peripheral blood mononuclear cell analyses, fresh whole blood samples were analyzed directly. Results Our study revealed a marked shift in the myeloid-lymphoid balance, characterized by elevated neutrophils, eosinophils, and classical monocytes that correlated with disease severity, alongside reduced CD8 + T cells and circulating T follicular helper cells. Transcriptional profiling identified oxidative stress pathways, T cell suppression, and aberrant natural killer (NK) cell activation as hallmarks of advanced COPD. Notably,...