{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T17:22:08Z","timestamp":1792430528945,"version":"4.5.0"},"reference-count":111,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"776","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2024,12,4]]},"abstract":"<jats:p>\n            Neurological injury drives most deaths and morbidity among patients hospitalized for out-of-hospital cardiac arrest (OHCA). Despite its clinical importance, there are no effective pharmacological therapies targeting post\u2013cardiac arrest (CA) neurological injury. Here, we analyzed circulating immune cells from a large cohort of patients with OHCA, finding that lymphopenia independently associated with poor neurological outcomes. Single-cell RNA sequencing of immune cells showed that T cells with features of both innate T cells and natural killer (NK) cells were increased in patients with favorable neurological outcomes. We more specifically identified an early increase in circulating diverse NKT (dNKT) cells in a separate cohort of patients with OHCA who had good neurological outcomes. These cells harbored a diverse T cell receptor repertoire but were consistently specific for sulfatide antigen. In mice, we found that sulfatide-specific dNKT cells trafficked to the brain after CA and resuscitation. In the brains of mice lacking NKT cells (\n            <jats:italic>Cd1d<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            ), we observed increased inflammatory chemokine and cytokine expression and accumulation of macrophages when compared with wild-type mice.\n            <jats:italic>Cd1d<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice also had increased neuronal injury, neurological dysfunction, and worse mortality after CA. To therapeutically enhance dNKT cell activity, we treated mice with sulfatide lipid after CA, showing that it improved neurological function. Together, these data show that sulfatide-specific dNKT cells are associated with good neurological outcomes after clinical OHCA and are neuroprotective in mice after CA. Strategies to enhance the number or function of dNKT cells may thus represent a treatment approach for CA.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.adq5796","type":"journal-article","created":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T18:58:53Z","timestamp":1733338733000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":15,"title":["Diverse NKT cells regulate early inflammation and neurological outcomes after cardiac arrest and resuscitation"],"prefix":"10.1126","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7435-6534","authenticated-orcid":true,"given":"Tomoyoshi","family":"Tamura","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA."},{"name":"Harvard Medical School, Boston, MA 02115, USA."},{"name":"Department of Emergency and Critical Care Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2458-2522","authenticated-orcid":true,"given":"Changde","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Computational Biology, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA."},{"name":"Stem Cell Biology Program, Division of Hematology and Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35233, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3940-5617","authenticated-orcid":true,"given":"Ana B.","family":"Villase\u00f1or-Altamirano","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA."},{"name":"Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5094-8864","authenticated-orcid":true,"given":"Kohei","family":"Yamada","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA."},{"name":"Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0961-1532","authenticated-orcid":true,"given":"Kohei","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA 02115, USA."},{"name":"Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA 02114, 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Seethala Y. Tesfaigzi A. J. Weissman B. M. Baron F. Ichinose K. M. Berg E. A. Bohula D. A. Morrow X. Chen E. Y. Kim Immunology of Cardiac Arrest Network (I-CAN) Single-cell transcriptomics reveal hyperacute cytokine and immune checkpoint axis in patients with poor neurological outcomes after cardiac arrest. bioRxiv 487033 [Preprint] (2022). 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