Single-cell RNA sequencing–based analysis of alveolar type II cell heterogeneity and immune regulatory features in chronic obstructive pulmonary disease_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

AI Yu ¹ , LI Hui ¹ , LIU Boya ¹ , ZHANG Jiachi ¹ , LI Peijun ¹ ,  LIU Xiaodan ^1,2,3

1. School of Rehabilitation Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P. R. China;
2. Engineering Research Center of Intelligent Rehabilitation of Traditional Chinese Medicine, Ministry of Education, Shanghai 201203, P. R. China;
3. Institute of Rehabilitation Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai 201203, P. R. China;

Corresponding?author：

LIU Xiaodan, Email: hzhp403@126.com

Keywords：

Chronic obstructive pulmonary disease; alveolar type II cells; single-cell RNA sequencing; cell–cell interaction

DOI：

10.7507/1671-6205.202601111

Video：

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Objective To investigate the heterogeneity of lung epithelial cells, particularly alveolar type II (AT2) cells, in chronic obstructive pulmonary disease (COPD), and to explore their potential interactions with immune cells.Methods Single-cell RNA sequencing (scRNA-seq) was performed to systematically analyze 57,879 lung-derived cells obtained from patients with mild to moderate COPD and age-matched control individuals. Major cell types were identified through cell clustering and annotation. AT2 cells were further subdivided into distinct subpopulations, and differential gene expression analysis, functional enrichment analysis, pseudotime trajectory analysis, and cell–cell communication analysis were conducted to characterize their transcriptional features, differentiation trajectories, and interaction patterns with immune cells.Results Single-cell analysis identified major cell populations, including epithelial, immune, stromal, and endothelial cells. Compared with controls, AT2 cells from COPD patients exhibited pronounced heterogeneity, with a significantly increased proportion of an inflammation-associated AT2 subpopulation characterized by high expression of complement component C3. Functional enrichment analysis revealed that this subpopulation was significantly enriched in complement activation and inflammatory response–related pathways. Cell–cell communication analysis suggested that this inflammatory AT2 subpopulation may aberrantly interact with macrophages via the C3–ITGAX/ITGB2 signaling axis, potentially contributing to the formation and maintenance of the chronic inflammatory microenvironment in COPD.Conclusions At the single-cell transcriptomic level, this study identifies a novel inflammation-associated AT2 cell subpopulation in COPD lung tissue and suggests its potential involvement in immune regulation through complement-mediated AT2–macrophage interactions. These findings provide new insights into the pathogenesis of COPD and offer a theoretical basis for the exploration of potential targeted therapeutic strategies.

Citation： AI Yu, LI Hui, LIU Boya, ZHANG Jiachi, LI Peijun, LIU Xiaodan. Single-cell RNA sequencing–based analysis of alveolar type II cell heterogeneity and immune regulatory features in chronic obstructive pulmonary disease. Chinese Journal of Respiratory and Critical Care Medicine, 2026, 25(8): 555-565. doi: 10.7507/1671-6205.202601111 Copy

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Chinese Journal of Respiratory and Critical Care Medicine

Single-cell RNA sequencing–based analysis of alveolar type II cell heterogeneity and immune regulatory features in chronic obstructive pulmonary disease

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