{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T10:56:44Z","timestamp":1791457004289,"version":"4.3.4"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":13,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"DOI":"10.1038\/s42003-026-10995-2","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:05:52Z","timestamp":1790359552000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Expanded proinflammatory CD4 T cells expressing toll like receptor 4 in trauma associated acute lung injury"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4851-3855","authenticated-orcid":false,"given":"Priyanka","family":"Hastak","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9321-8660","authenticated-orcid":false,"given":"Christopher R.","family":"Andersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5395-3296","authenticated-orcid":false,"given":"Phoebe","family":"Crammond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zong-Hong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6617-5995","authenticated-orcid":false,"given":"Chansavath","family":"Phetsouphanh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"van Bockel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calum","family":"Walsh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise M.","family":"Judd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0150-123X","authenticated-orcid":false,"given":"Timothy P.","family":"Stinear","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aayushma","family":"Lohani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swosti","family":"Shrestha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9384-2447","authenticated-orcid":false,"given":"Raymond","family":"Louie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances","family":"Bass","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Delaney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Hammond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3234-5244","authenticated-orcid":false,"given":"Balasubramanian","family":"Venkatesh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2785-5864","authenticated-orcid":false,"given":"Simon","family":"Finfer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicodemus","family":"Tedla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0009-3337","authenticated-orcid":false,"given":"Anthony D.","family":"Kelleher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5329-9072","authenticated-orcid":false,"given":"Sarah C.","family":"Sasson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"10995_CR1","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1001\/jama.2016.0291","volume":"315","author":"G Bellani","year":"2016","unstructured":"Bellani, G. et al. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA 315, 788\u2013800 (2016).","journal-title":"JAMA"},{"key":"10995_CR2","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1046\/j.1365-2044.2003.03287.x","volume":"58","author":"M Hughes","year":"2003","unstructured":"Hughes, M. et al. Acute respiratory distress syndrome: an audit of incidence and outcome in Scottish intensive care units. Anaesthesia 58, 838\u2013845 (2003).","journal-title":"Anaesthesia"},{"key":"10995_CR3","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1007\/s00134-003-2022-6","volume":"30","author":"C Brun-Buisson","year":"2004","unstructured":"Brun-Buisson, C. et al. Epidemiology and outcome of acute lung injury in European intensive care units. Intensive Care Med. 30, 51\u201361 (2004).","journal-title":"Intensive Care Med."},{"key":"10995_CR4","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1164\/ajrccm.165.4.2101124","volume":"165","author":"AD Bersten","year":"2002","unstructured":"Bersten, A. D. et al. Incidence and mortality of acute lung injury and the acute respiratory distress syndrome in three Australian States. Am. J. Respir. Crit. Care Med. 165, 443\u2013448 (2002).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10995_CR5","doi-asserted-by":"publisher","first-page":"2091","DOI":"10.1016\/j.rmed.2007.05.021","volume":"101","author":"J Wind","year":"2007","unstructured":"Wind, J. et al. Epidemiology of acute lung injury and acute respiratory distress syndrome in The Netherlands: a survey. Respir. Med. 101, 2091\u20132098 (2007).","journal-title":"Respir. Med."},{"key":"10995_CR6","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1056\/NEJM200005043421801","volume":"342","author":"RG Brower","year":"2000","unstructured":"Brower, R. G. et al. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N. Engl. J. Med. 342, 1301\u20131308 (2000).","journal-title":"N. Engl. J. Med."},{"key":"10995_CR7","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1016\/S0140-6736(22)01485-4","volume":"400","author":"LDJ Bos","year":"2022","unstructured":"Bos, L. D. J. & Ware, L. B. Acute respiratory distress syndrome: causes, pathophysiology, and phenotypes. Lancet 400, 1145\u20131156 (2022).","journal-title":"Lancet"},{"key":"10995_CR8","doi-asserted-by":"publisher","first-page":"2159","DOI":"10.1056\/NEJMoa1214103","volume":"368","author":"C Gu\u00e9rin","year":"2013","unstructured":"Gu\u00e9rin, C. et al. Prone positioning in severe acute respiratory distress syndrome. N. Engl. J. Med. 368, 2159\u20132168 (2013).","journal-title":"N. Engl. J. Med."},{"key":"10995_CR9","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/s41572-019-0069-0","volume":"5","author":"MA Matthay","year":"2019","unstructured":"Matthay, M. A. et al. Acute respiratory distress syndrome. Nat. Rev. Dis. Prim. 5, 18 (2019).","journal-title":"Nat. Rev. Dis. Prim."},{"key":"10995_CR10","doi-asserted-by":"crossref","unstructured":"RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with Covid-19. N. Engl. J. Med. 384, 693\u2013704 (2021).","DOI":"10.1056\/NEJMoa2021436"},{"key":"10995_CR11","doi-asserted-by":"publisher","first-page":"1407","DOI":"10.1016\/S2213-2600(21)00331-3","volume":"9","author":"VC Marconi","year":"2021","unstructured":"Marconi, V. C. et al. Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial.  Lancet Respir. Med. 9, 1407\u20131418 (2021).","journal-title":"Lancet Respir. Med."},{"key":"10995_CR12","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1056\/NEJMoa2101643","volume":"385","author":"PO Guimar\u00e3es","year":"2021","unstructured":"Guimar\u00e3es, P. O. et al. Tofacitinib in Patients Hospitalized with Covid-19 Pneumonia. N. Engl. J. Med. 385, 406\u2013415 (2021).","journal-title":"N. Engl. J. Med."},{"key":"10995_CR13","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1056\/NEJMoa2030340","volume":"384","author":"C Salama","year":"2021","unstructured":"Salama, C. et al. Tocilizumab in patients hospitalized with Covid-19 pneumonia. N. Engl. J. Med. 384, 20\u201330 (2021).","journal-title":"N. Engl. J. Med."},{"key":"10995_CR14","doi-asserted-by":"crossref","unstructured":"Interleukin-6 receptor antagonists in critically ill patients with Covid-19. N. Engl. J. Med. 384, 1491\u20131502 (2021).","DOI":"10.1056\/NEJMoa2100433"},{"key":"10995_CR15","doi-asserted-by":"publisher","DOI":"10.1186\/s13613-024-01360-9","volume":"14","author":"M Ostermann","year":"2024","unstructured":"Ostermann, M. et al. Biomarkers in acute kidney injury. Ann. Intensive Care 14, 145 (2024).","journal-title":"Ann. Intensive Care"},{"key":"10995_CR16","first-page":"1","volume":"28","author":"N Alipanah","year":"2022","unstructured":"Alipanah, N. & Calfee, C. S. Phenotyping in acute respiratory distress syndrome: state of the art and clinical implications. Curr. Opin. Crit. Care 28, 1\u20138 (2022).","journal-title":"Curr. Opin. Crit. Care"},{"key":"10995_CR17","doi-asserted-by":"publisher","first-page":"1244","DOI":"10.2741\/4176","volume":"18","author":"R Hu","year":"2013","unstructured":"Hu, R. et al. The role of TLR4 in the pathogenesis of indirect acute lung injury. Front. Biosci. 18, 1244\u20131255 (2013).","journal-title":"Front. Biosci."},{"key":"10995_CR18","doi-asserted-by":"publisher","first-page":"1729","DOI":"10.1016\/j.chest.2021.07.009","volume":"160","author":"YA Khan","year":"2021","unstructured":"Khan, Y. A., Fan, E. & Ferguson, N. D. Precision medicine and heterogeneity of treatment effect in therapies for ARDS. Chest 160, 1729\u20131738 (2021).","journal-title":"Chest"},{"key":"10995_CR19","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1164\/rccm.202311-2086SO","volume":"210","author":"AC Gordon","year":"2024","unstructured":"Gordon, A. C. et al. From ICU syndromes to ICU subphenotypes: consensus report and recommendations for developing precision medicine in the ICU. Am. J. Respir. Crit. Care Med. 210, 155\u2013166 (2024).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10995_CR20","doi-asserted-by":"publisher","first-page":"100233","DOI":"10.1016\/j.xpro.2020.100233","volume":"1","author":"E De Domenico","year":"2020","unstructured":"De Domenico, E. et al. Optimized workflow for single-cell transcriptomics on infectious diseases including COVID-19. STAR Protoc. 1, 100233 (2020).","journal-title":"STAR Protoc."},{"key":"10995_CR21","doi-asserted-by":"crossref","unstructured":"Krishnan, U. et al. Presence of gastric pepsinogen in the trachea is associated with altered inflammation and microbial composition. Infect. Immun. 88, e00455-20 (2020).","DOI":"10.1128\/IAI.00455-20"},{"key":"10995_CR22","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1214\/aoms\/1177730491","volume":"18","author":"HB Mann","year":"1947","unstructured":"Mann, H. B. & Whitney, D. R. On a test of whether one of two random variables is stochastically larger than the other.  Ann. Math. Stat. 18, 50\u201360 (1947). 11.","journal-title":"Ann. Math. Stat."},{"key":"10995_CR23","doi-asserted-by":"crossref","unstructured":"Dunn, O. J. Multiple comparisons among means. J. Am. Stat. Assoc. 56, 52\u201364 (1961).","DOI":"10.1080\/01621459.1961.10482090"},{"key":"10995_CR24","doi-asserted-by":"publisher","first-page":"99","DOI":"10.2307\/3001913","volume":"5","author":"JW Tukey","year":"1949","unstructured":"Tukey, J. W. Comparing individual means in the analysis of variance. Biometrics 5, 99\u2013114 (1949).","journal-title":"Biometrics"},{"key":"10995_CR25","doi-asserted-by":"crossref","unstructured":"Nori, S. R. C. et al. Profiling of vaginal Lactobacillus jensenii isolated from preterm and full-term pregnancies reveals strain-specific factors relating to host interaction. Microb. Genom. 9, 001137 (2023).","DOI":"10.1099\/mgen.0.001137"},{"key":"10995_CR26","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1038\/s41592-022-01520-4","volume":"19","author":"KD Curry","year":"2022","unstructured":"Curry, K. D. et al. Emu: species-level microbial community profiling of full-length 16S rRNA Oxford Nanopore sequencing data. Nat. Methods 19, 845\u2013853 (2022).","journal-title":"Nat. Methods"},{"key":"10995_CR27","unstructured":"Team, R. C. R: A Language and Environment for Statistical Computing (R Foundation for Statistical Computing, Vienna, Austria, 2023)."},{"key":"10995_CR28","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-018-0605-2","volume":"6","author":"NM Davis","year":"2018","unstructured":"Davis, N. M. et al. Simple statistical identification and removal of contaminant sequences in marker-gene and metagenomics data. Microbiome 6, 226 (2018).","journal-title":"Microbiome"},{"key":"10995_CR29","unstructured":"Oksanen, J. et al. vegan: Community Ecology Package. R package version 2.6-4 (2022)."},{"key":"10995_CR30","unstructured":"A, K., rstatix: Pipe-Friendly Framework for Basic Statistical Tests: R package version 0.7.2 (2023)."},{"key":"10995_CR31","unstructured":"M, H., RVAideMemoire: Testing and Plotting Procedures for Biostatistics. R package version 0.9-83-3 (203)."},{"key":"10995_CR32","doi-asserted-by":"crossref","unstructured":"ARDS Definition Task Force. Acute respiratory distress syndrome: the Berlin definition. JAMA 307, 2526\u20132533 (2012).","DOI":"10.1001\/jama.2012.5669"},{"key":"10995_CR33","doi-asserted-by":"publisher","first-page":"1092799","DOI":"10.3389\/fimmu.2023.1092799","volume":"14","author":"S Unterberger","year":"2023","unstructured":"Unterberger, S. et al. Multiple TLRs elicit alternative NLRP3 inflammasome activation in primary human monocytes independent of RIPK1 kinase activity. Front. Immunol. 14, 1092799 (2023).","journal-title":"Front. Immunol."},{"key":"10995_CR34","doi-asserted-by":"publisher","first-page":"2026","DOI":"10.3389\/fimmu.2026.1761361","volume":"17","author":"P Crammond","year":"2026","unstructured":"Crammond, P. et al. Taking its TOLL: the role of toll-like receptor 4 in human health and disease, and its potential as a therapeutic target. Front. Immunol. 17, 2026 (2026).","journal-title":"Front. Immunol."},{"key":"10995_CR35","doi-asserted-by":"publisher","first-page":"610682","DOI":"10.3389\/fgene.2020.610682","volume":"11","author":"A Zarinsefat","year":"2020","unstructured":"Zarinsefat, A. et al. Single-cell RNA sequencing of tocilizumab-treated peripheral blood mononuclear cells as an in vitro model of inflammation. Front. Genet. 11, 610682 (2020).","journal-title":"Front. Genet."},{"key":"10995_CR36","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1124\/mol.110.068064","volume":"79","author":"N Matsunaga","year":"2011","unstructured":"Matsunaga, N. et al. TAK-242 (resatorvid), a small-molecule inhibitor of Toll-like receptor (TLR) 4 signaling, binds selectively to TLR4 and interferes with interactions between TLR4 and its adaptor molecules. Mol. Pharm. 79, 34\u201341 (2011).","journal-title":"Mol. Pharm."},{"key":"10995_CR37","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18443-3","volume":"11","author":"A Volchuk","year":"2020","unstructured":"Volchuk, A. et al. Indirect regulation of HMGB1 release by gasdermin D. Nat. Commun. 11, 4561 (2020).","journal-title":"Nat. Commun."},{"key":"10995_CR38","doi-asserted-by":"crossref","unstructured":"Bhushan, V. et al. Nigericin-triggered phosphodynamics in inflammasome formation and pyroptosis. Proteomics e70030 (2025).","DOI":"10.1002\/pmic.70030"},{"key":"10995_CR39","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1038\/s12276-020-00486-7","volume":"52","author":"H-G Lee","year":"2020","unstructured":"Lee, H.-G., Cho, M.-J. & Choi, J.-M. Bystander CD4+ T cells: crossroads between innate and adaptive immunity. Exp. Mol. Med. 52, 1255\u20131263 (2020).","journal-title":"Exp. Mol. Med."},{"key":"10995_CR40","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1016\/S2213-2600(14)70097-9","volume":"2","author":"CS Calfee","year":"2014","unstructured":"Calfee, C. S. et al. Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials. Lancet Respir. Med. 2, 611\u2013620 (2014).","journal-title":"Lancet Respir. Med."},{"key":"10995_CR41","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1016\/S2213-2600(18)30177-2","volume":"6","author":"CS Calfee","year":"2018","unstructured":"Calfee, C. S. et al. Acute respiratory distress syndrome subphenotypes and differential response to simvastatin: secondary analysis of a randomised controlled trial. Lancet Respir. Med. 6, 691\u2013698 (2018).","journal-title":"Lancet Respir. Med."},{"key":"10995_CR42","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1016\/j.phrs.2018.08.014","volume":"135","author":"A Bahrami","year":"2018","unstructured":"Bahrami, A. et al. Effect of statins on toll-like receptors: a new insight to pleiotropic effects. Pharmacol. Res. 135, 230\u2013238 (2018).","journal-title":"Pharmacol. Res."},{"key":"10995_CR43","doi-asserted-by":"publisher","first-page":"705080","DOI":"10.3389\/fimmu.2021.705080","volume":"12","author":"KA Shirey","year":"2021","unstructured":"Shirey, K. A., Blanco, J. C. G. & Vogel, S. N. Targeting TLR4 signaling to blunt viral-mediated acute lung injury. Front. Immunol. 12, 705080 (2021).","journal-title":"Front. Immunol."}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-026-10995-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-026-10995-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-026-10995-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T10:37:42Z","timestamp":1791455862000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-026-10995-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,25]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["10995"],"URL":"https:\/\/doi.org\/10.1038\/s42003-026-10995-2","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,25]]},"assertion":[{"value":"6 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 September 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 September 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"1314"}}