ArticleInternational journal of chronic obstructive pulmonary disease2026
Single-Cell Transcriptomics Reveals Macrophage Dysfunction and cDC2 Activation in COPD: Candidate Biomarkers for Individualized Nursing Care.
Article in International journal of chronic obstructive pulmonary disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Chronic obstructive pulmonary disease (COPD) is a leading cause of global morbidity and mortality driven by dysregulated airway immunity. Macrophages and conventional type 2 dendritic cells (cDC2s) are central orchestrators of this process, yet their transcriptional heterogeneity at single-cell resolution and relationship to clinical severity remain incompletely characterized. Methods: We performed integrative analysis of single-cell RNA sequencing (scRNA-seq) data from 45,708 lung immune cells combined with bulk microarray data from 236 lung tissue samples. After Harmony-based batch correction and graph-based clustering, 11 immune cell populations were annotated. Pseudobulk differential expression was performed using DESeq2, functional enrichment by gene set enrichment analysis against MSigDB Hallmark, KEGG, and GO:BP gene sets, and protein-protein interaction (PPI) network analysis using STRINGdb. Clinical correlation used Spearman rank correlation between hub gene expression and GOLD stage, FEV1% predicted, emphysema index, and DLCO%. Results: Macrophages were depleted in COPD while cDC2s were 4.7-fold expanded. Macrophages exhibited 1,268 differentially expressed genes dominated by IFN-γ response (NES = 2.60) and TNFα/NF-κB activation (NES = 2.41), with concurrent loss of mitochondrial function (NES = -2.40) and lysosomal acidification (NES = -2.25). cDC2s showed strong TNFα/NF-κB (NES = 2.88) and JAK-STAT (NES = 2.36) activation. PPI analysis identified IFNG, IL1B, CCR7, GZMB, and NFKB1 as central hubs. Cross-dataset validation confirmed LRG1, CCR7, IRF4, and TIMP1 as clinically correlated biomarkers. Conclusion: This study identifies coordinated macrophage M1 polarization, metabolic dysfunction, and impaired efferocytosis in COPD, with cDC2-driven adaptive immune amplification. Eleven candidate biomarkers are proposed as targets for individualized nursing monitoring and precision respiratory care.
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