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<p>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&#xa0;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&#xa0;as a distinguishing feature of E-COPD. &#xa0;Compared to controls,&#xa0;glucocorticoid receptor NR3C1 CD4 T cells were enriched in NE-COPD but were reduced in E-COPD. Interactions between macrophages and NR3C1<sup>+</sup> 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 CXCR6<sup>high</sup> effector memory T cells positively correlated with preserved lung function in E-COPD but not in NE-COPD. These findings suggest that NR3C1<sup>+</sup> and CXCR6<sup>high</sup> 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&#xa0;opportunities.</p><p></p>

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Lung NR3C1+ and CXCR6high T cells distinguish immunopathogenesis of human emphysema

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月24日

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  • Yun Zhang,
  • Maor Sauler,
  • David B. Corry,
  • Scott A. Ochsner,
  • Sarah Perusich,
  • Li-Zhen Song,
  • Joshua Malo,
  • Raul San Jose Estepar,
  • Francesca Polverino,
  • Farrah Kheradmand

摘要

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.