{"doi":"10.1165/rcmb.2024-0201oc","title":"PD-L1 and PD-1 Are Associated with Clinical Outcomes and Alveolar Immune Cell Activation in Acute Respiratory Distress Syndrome","abstract":"Abstract The relationship between the PD-L1 (Programmed Death-Ligand 1)/PD-1 pathway, lung inflammation, and clinical outcomes in acute respiratory distress syndrome (ARDS) is poorly understood. We sought to determine whether PD-L1/PD-1 in the lung or blood is associated with ARDS and associated severity. We measured soluble PD-L1 (sPD-L1) in plasma and lower respiratory tract samples (ARDS1 [n = 59] and ARDS2 [n = 78]) or plasma samples alone (ARDS3 [n = 149]) collected from subjects with ARDS and tested for associations with mortality using multiple regression. We used mass cytometry to measure PD-L1/PD-1 expression and intracellular cytokine staining in cells isolated from BAL fluid (n = 18) and blood (n = 16) from critically ill subjects with or without ARDS enrolled from a fourth cohort. Higher plasma concentrations of sPD-L1 were associated with mortality in ARDS1, ARDS2, and ARDS3. In contrast, higher concentrations of sPD-L1 in the lung were either not associated with mortality (ARDS2) or were associated with survival (ARDS1). Alveolar PD-1POS T cells had more intracellular cytokine staining than PD-1NEG T cells. Subjects without ARDS had a higher ratio of PD-L1POS alveolar macrophages to PD-1POS T cells than subjects with ARDS. We conclude that sPD-L1 may have divergent cellular sources and/or functions in the alveolar versus blood compartments, given distinct associations with mortality. Alveolar leukocyte subsets defined by PD-L1 or PD-1 cell-surface expression have distinct cytokine secretion profiles, and the relative proportions of these subsets are associated with ARDS.","journal":"American Journal of Respiratory Cell and Molecular Biology","year":2024,"id":435472,"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":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9667,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":442159,"name":"Sarah E. 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Linzee Mabrey","orcid":"0000-0003-0263-9601","position":11,"is_corresponding":false},{"id":306544,"name":"Renee D. Stapleton","orcid":null,"position":12,"is_corresponding":false},{"id":432349,"name":"Uma Malhotra","orcid":"0000-0003-0132-0885","position":13,"is_corresponding":false},{"id":271012,"name":"Cate Speake","orcid":"0000-0003-1480-4272","position":14,"is_corresponding":false},{"id":108914,"name":"Jessica A. Hamerman","orcid":"0000-0001-5864-5299","position":15,"is_corresponding":false},{"id":654136,"name":"Sudhakar Pipavath","orcid":null,"position":16,"is_corresponding":false},{"id":15403,"name":"Laura Evans","orcid":"0000-0002-3176-6493","position":17,"is_corresponding":false},{"id":249666,"name":"Pavan K. Bhatraju","orcid":"0000-0002-2606-4366","position":18,"is_corresponding":false},{"id":1242670,"name":"Sihui Long","orcid":"0000-0002-4424-6374","position":19,"is_corresponding":false},{"id":253256,"name":"Mark M. 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