Language
English
Publication Date
9-24-2025
Journal
Communications Biology
DOI
10.1038/s42003-025-08698-1
PMID
40993192
PMCID
PMC12460644
PubMedCentral® Posted Date
9-24-2025
PubMedCentral® Full Text Version
Post-print
Abstract
There is a significant knowledge gap in how T cells promote emphysema in smokers with chronic obstructive pulmonary disease (COPD). Single-cell RNA sequencing (scRNA seq) analysis of human samples and relevant clinical data can provide new mechanistic insights into disease pathogenesis. We generated a human lung scRNA seq dataset with extensive disease characteristic annotation and analyzed a second independent scRNA seq dataset to examine the pathophysiological role of T cells in emphysema. Comparisons of pulmonary immune landscapes in emphysematous (E)-COPD, non-emphysematous (NE)-COPD, and control showed positive enrichment of T cells in E-COPD. Pathway analyses identified upregulated inflammatory states in CD4 T cells as a distinguishing feature of E-COPD. Compared to controls, glucocorticoid receptor NR3C1 CD4 T cells were enriched in NE-COPD but were reduced in E-COPD. Interactions between macrophages and NR3C1+ CD4 T cell subsets via CXCL signaling were strongly predicted in E-COPD but were absent in NE-COPD and control. The relative abundance of CD4 CXCR6high effector memory T cells positively correlated with preserved lung function in E-COPD but not in NE-COPD. These findings suggest that NR3C1+ and CXCR6high effector memory subsets of CD4 T cells distinguish the immune-pathophysiological features of emphysema in human lungs. Targeting relevant T cell subsets in emphysema might provide new therapeutic opportunities.
Keywords
Humans, Lung, Pulmonary Emphysema, Receptors, CXCR6, Receptors, Glucocorticoid, Pulmonary Disease, Chronic Obstructive, Male, CD4-Positive T-Lymphocytes, Female, Middle Aged, Aged, Single-Cell Analysis, Chronic inflammation, Predictive markers
Published Open-Access
yes
Recommended Citation
Zhang, Yun; Sauler, Maor; Corry, David B; et al., "Lung NR3C1+ and CXCR6high T Cells Distinguish Immunopathogenesis of Human Emphysema" (2025). Faculty and Staff Publications. 4649.
https://digitalcommons.library.tmc.edu/baylor_docs/4649
Graphical Abstract