{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T01:20:57Z","timestamp":1792718457698,"version":"4.5.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R35GM142481"],"award-info":[{"award-number":["R35GM142481"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R35GM1480881"],"award-info":[{"award-number":["R35GM1480881"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UM1TR004405"],"award-info":[{"award-number":["UM1TR004405"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32TR004385"],"award-info":[{"award-number":["T32TR004385"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research Career Scientist","award":["IK6BX006192"],"award-info":[{"award-number":["IK6BX006192"]}]},{"DOI":"10.13039\/100000738","name":"Department of Veterans Affairs","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Severe trauma triggers a dynamic disturbance of immune function that can progress from early hyperinflammation to prolonged dysregulation, increasing patient vulnerability to infection and chronic critical illness (CCI). To identify immune features linked to different postinjury clinical trajectories, we prospectively evaluated severely injured trauma patients and categorized them as rapid recovery, intermediate, or CCI based on clinical outcome by day 14 of intensive care unit admission. CCI patients developed infections earlier and more frequently than rapid recovery or intermediate patients, with nearly one-third experiencing their first infection (primarily pneumonia) within 4\u2009d of intensive care unit admission and &amp;gt;80% did so within 8\u2009d. Immune profiling showed trauma-associated alterations across all groups, including neutrophilia and early T cell lymphopenia. However, CCI patients exhibited a distinct immunophenotype characterized by elevated neutrophil counts, recovery of total CD3+ T cells by day 7, preserved inducible interferon \u03b3 (IFN\u03b3) production, and a selective expansion of CD4+ T helper 17 (Th17) cells. Functional assays revealed sustained or amplified T cell cytokine responses in CCI patients, including persistent IFN\u03b3 and interleukin (IL)-17A production. Plasma cytokine analysis further demonstrated prolonged elevation of IL-17A, IL-17C, IFN\u03b3, and IL-10, indicating a mixed but enduring pro- and anti-inflammatory state. These findings suggest that CCI after trauma is not driven by classic immunosuppression, but rather is driven by an IL-17\u2013skewed immune program coupled with ineffective pathogen control. The persistent Th17\/neutrophil axis may contribute to heightened infection risk and progression to CCI, highlighting dysregulated IL-17\u2013mediated innate and adaptive circuits as a potential mechanism of ongoing immune dysfunction following severe trauma.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag125","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T04:02:32Z","timestamp":1782360152000},"source":"Crossref","is-referenced-by-count":4,"title":["Distinct immune trajectories after severe trauma identify a Th17-biased immunophenotype in chronic critical illness"],"prefix":"10.1093","volume":"215","author":[{"given":"Caleb Y","family":"Kim","sequence":"first","affiliation":[{"name":"Microbiology, Immunology, and Cancer Biology Graduate Program, University of Minnesota , Minneapolis, MN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyuan","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Washington , Seattle, WA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Mirabadi","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Washington , Seattle, WA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5608-7167","authenticated-orcid":false,"given":"Shuhua","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Washington , Seattle, WA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelsey","family":"Scherler","sequence":"additional","affiliation":[{"name":"Institute for Systems Biology , Seattle, WA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathie-Anne","family":"Walters","sequence":"additional","affiliation":[{"name":"Institute for Systems Biology , Seattle, WA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grant","family":"O\u2019Keefe","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Washington , Seattle, WA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7205-9859","authenticated-orcid":false,"given":"Thomas S","family":"Griffith","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Minnesota , Minneapolis, MN,","place":["United States"]},{"name":"Center for Immunology, University of Minnesota , Minneapolis, MN,","place":["United States"]},{"name":"Minneapolis VA Health Care System Department of Urology, , Minneapolis, MN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott C","family":"Brakenridge","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Washington , Seattle, WA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"2026090710424070600_vkag125-B1","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1189\/jlb.0212072","article-title":"Trauma equals danger\u2014damage control by the immune system","volume":"92","author":"Stoecklein","year":"2012","journal-title":"J Leukoc Biol."},{"key":"2026090710424070600_vkag125-B2","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.3389\/fimmu.2018.01511","article-title":"Chronic critical illness and the persistent inflammation, immunosuppression, and catabolism syndrome","volume":"9","author":"Hawkins","year":"2018","journal-title":"Front Immunol."},{"key":"2026090710424070600_vkag125-B3","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1097\/CCM.0000000000002697","article-title":"The epidemiology of chronic critical illness after severe traumatic injury at two level-one trauma centers","volume":"45","author":"Mira","year":"2017","journal-title":"Crit Care Med."},{"key":"2026090710424070600_vkag125-B4","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1097\/TA.0000000000004671","article-title":"Attenuated interferon-gamma following injury is associated with chronic critical illness","volume":"99","author":"Cuschieri","year":"2025","journal-title":"J Trauma Acute Care Surg."},{"key":"2026090710424070600_vkag125-B5","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1186\/s13054-016-1341-2","article-title":"Early changes within the lymphocyte population are associated with the development of multiple organ dysfunction syndrome in trauma patients","volume":"20","author":"Manson","year":"2016","journal-title":"Crit. 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