Single-cell analysis of COPD: Microenvironmental interactions driven by immune-fibrotic imbalance

Chronic obstructive pulmonary disease (COPD) is a respiratory disease with a high degree of cellular heterogeneity and molecular complexity, characterized pathologically by persistent airflow limitation and an inflammatory-tissue remodeling cascade involving multiple cell types. Traditional transcriptomics lack the resolution to precisely define cell subpopulation roles in COPD. Single-cell RNA sequencing (scRNA-seq) overcomes this limitation by enabling high-resolution analysis of cell-type-specific mechanisms in COPD. A total of 101,009 cells from three scRNA-seq datasets were integrated to profile COPD-related molecular features and cell interactions at single-cell resolution. Analysis identified four major cell types and 17 distinct cell subtypes. Cell–cell communication analysis revealed a significant reduction in signaling activity of macrophages and fibroblasts, whereas certain immune cells exhibited enhanced signaling, suggesting that immune dysregulation plays a pivotal role in COPD pathogenesis. Further analysis focused on macrophage-dominant myeloid cells and fibroblasts, uncovering their critical roles in inflammation modulation and fibrosis progression. Meanwhile, this study also identified 19 chemicals that may influence COPD progression by modulating cellular gene expression. This study provides an important molecular basis for unraveling the cell-cell interaction network of COPD and elucidating the mechanism of each cell subpopulation in the disease process.