{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T05:19:59Z","timestamp":1787721599000,"version":"build-2784847793"},"reference-count":50,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["309168\/Z\/24\/Z"],"award-info":[{"award-number":["309168\/Z\/24\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"award":["309168\/Z\/24\/Z"],"award-info":[{"award-number":["309168\/Z\/24\/Z"]}],"id":[{"id":"https:\/\/ror.org\/029chgv08","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Department of Health","award":["HICFR7405"],"award-info":[{"award-number":["HICFR7405"]}]},{"DOI":"10.13039\/501100000272","name":"National Institute of Health Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/00spd2n27","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Early Career Award","doi-asserted-by":"publisher","award":["309168\/Z\/24\/Z"],"award-info":[{"award-number":["309168\/Z\/24\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The cellular immune response underlying post-injury multiple organ dysfunction syndrome (MODS) remains incompletely described. We hypothesized that early perturbations in innate lymphocyte behavior are critical to the development of MODS in trauma patients. To address this, we examined lymphocyte subsets in a prospective cohort of major trauma patients recruited at a single major trauma hospital. Circulating lymphocytes were profiled with flow cytometry in serial samples drawn within the hyperacute (\u22642 h) and acute (24 h, 72 h) post-injury periods. Plasma levels of specific mediators derived from innate lymphocytes were also measured in a larger cohort. We observed a marked hyperacute increase in circulating NK (particularly the CD56dim subset) and V\u03b41 cells that were associated with MODS or early mortality. Absolute counts of NK activation markers CD69 and NKG2D were also higher in patients with adverse outcomes, although the proportion of NK cells expressing NKG2D was reduced. Exploratory cluster analyses of NK activating and inhibiting receptors identified patient groups with differing injury characteristics and outcomes. In plasma, patients who developed MODS had significantly higher levels of NK-associated cytotoxic mediators and cytokines. Collectively, these data indicate a specific pattern of hyperacute NK cell activation after major trauma that is characterized by a pattern consistent with cytotoxic lymphocyte activation and is associated with clinical outcome.<\/jats:p>","DOI":"10.3390\/biom16091228","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:07:53Z","timestamp":1787566073000},"page":"1228","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Natural Killer Cells Dominate the Hyperacute Lymphocyte Response to Major Trauma and Are Associated with Organ Dysfunction"],"prefix":"10.3390","volume":"16","author":[{"given":"Joanna M.","family":"Shepherd","sequence":"first","affiliation":[{"name":"Centre for Trauma Sciences, Blizard Institute, School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK"},{"name":"Major Trauma Department, St Mary\u2019s Hospital, Imperial College Healthcare NHS Trust, London W2 1NY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1013-8865","authenticated-orcid":false,"given":"Lucy R.","family":"Gibb","sequence":"additional","affiliation":[{"name":"Centre for Trauma Sciences, Blizard Institute, School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3854-1748","authenticated-orcid":false,"given":"Hew D. T.","family":"Torrance","sequence":"additional","affiliation":[{"name":"Section of Anaesthetics, Pain Medicine & Intensive Care, Department of Surgery & Cancer, Faculty of Medicine, Imperial College London, London W2 1NY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Manson","sequence":"additional","affiliation":[{"name":"Gloucestershire Hospitals NHS Foundation Trust, Gloucester GL1 3NN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Pennington","sequence":"additional","affiliation":[{"name":"Centre for Immunobiology and Infection, Blizard Institute, School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Vulliamy","sequence":"additional","affiliation":[{"name":"Centre for Trauma Sciences, Blizard Institute, School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK"},{"name":"Major Trauma Department, Royal London Hospital, Barts Health NHS Trust, London E1 1FR, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0643-8866","authenticated-orcid":false,"given":"Karim","family":"Brohi","sequence":"additional","affiliation":[{"name":"Centre for Trauma Sciences, Blizard Institute, School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK"},{"name":"Major Trauma Department, Royal London Hospital, Barts Health NHS Trust, London E1 1FR, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/s41590-018-0064-8","article-title":"Innate immune responses to trauma","volume":"19","author":"Lambris","year":"2018","journal-title":"Nat. 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