{"doi":"10.1038/s42003-025-08698-1","title":"Lung NR3C1+ and CXCR6high T cells distinguish immunopathogenesis of human emphysema","abstract":"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 CXCR6 high effector memory T cells positively correlated with preserved lung function in E-COPD but not in NE-COPD. These findings suggest that NR3C1 + and CXCR6 high 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.","journal":"Communications Biology","year":2025,"id":528918,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9142,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":377051,"name":"Maor Sauler","orcid":"0000-0001-5240-7978","position":1,"is_corresponding":false},{"id":325692,"name":"David B. Corry","orcid":"0000-0001-9729-1016","position":2,"is_corresponding":false},{"id":944338,"name":"Scott A. Ochsner","orcid":"0000-0003-1099-7863","position":3,"is_corresponding":false},{"id":1407646,"name":"Sarah Perusich","orcid":null,"position":4,"is_corresponding":false},{"id":1407647,"name":"Li-zhen Song","orcid":null,"position":5,"is_corresponding":false},{"id":557629,"name":"Joshua Malo","orcid":"0000-0003-0644-7754","position":6,"is_corresponding":false},{"id":267137,"name":"Raúl San Jośe Estépar","orcid":"0000-0002-3677-1996","position":7,"is_corresponding":false},{"id":232045,"name":"Francesca Polverino","orcid":"0000-0001-9686-5698","position":8,"is_corresponding":false},{"id":232202,"name":"Farrah Kheradmand","orcid":"0000-0001-5343-103X","position":9,"is_corresponding":false},{"id":698436,"name":"Yun Zhang","orcid":"0000-0002-1704-7775","position":0,"is_corresponding":true}],"reference_count":94,"raw_metadata":null,"created_at":"2026-07-19T02:50:52.565868Z","pmid":"40993192","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}