{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T07:16:00Z","timestamp":1788419760594,"version":"build-2803163510"},"reference-count":84,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Sepsis is increasingly recognized as a dynamic immune disorder in which early hyperinflammation may coexist with or progress to profound immunosuppression. T-cell exhaustion is a central feature of this immune paralysis and is characterized by lymphopenia, impaired proliferation, reduced effector cytokine production, inhibitory receptor upregulation, metabolic dysfunction, and defective antibacterial immunity. Recent studies have expanded the mechanistic landscape of sepsis-induced T-cell exhaustion beyond the classical PD-1\/PD-L1 axis. TIGIT-mediated suppression of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T-cell immunity, extracellular vesicle-associated PD-L1, TOX-independent exhaustion-like programming, dysregulated IL-17 production, mitochondrial dysfunction, and reduced glutaminase expression in CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells have emerged as important mechanisms. These findings indicate that septic T-cell exhaustion is not a direct replica of exhaustion in cancer or chronic viral infection, but a context-dependent and potentially reversible immune dysfunction state. Biomarkers such as PD-1\n                    <jats:sup>+<\/jats:sup>\n                    CD3\n                    <jats:sup>+<\/jats:sup>\n                    T cells, soluble PD-1\/PD-L1, IL-7, TIGIT, EV-PD-L1, and GLS may support patient stratification and dynamic immune monitoring. Immune-reversal strategies, including PD-1\/PD-L1 blockade, TIGIT inhibition, IL-7-based restoration, and metabolic reprogramming, require precise timing and individualized selection to restore host defense without aggravating inflammatory organ injury.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1897839","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T06:42:34Z","timestamp":1788417754000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["T cell exhaustion in sepsis: mechanisms, biomarkers, and immune-reversal strategies"],"prefix":"10.3389","volume":"17","author":[{"given":"Dongyang","family":"Li","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine, Qilu Hospital, Shandong University; Innovation Research Center for Sepsis and Multiple Organ Injury, Shandong University","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingren","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Beijing Chest Hospital, Capital Medical University","place":["Beijing, China"]},{"name":"Department of Cardiology, Beijing Tuberculosis and Thoracic Tumor Institute","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiyuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Qilu Hospital of Shandong University","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Qilu Hospital, Shandong University; Innovation Research Center for Sepsis and Multiple Organ Injury, Shandong University","place":["Jinan, Shandong, China"]},{"name":"Department of Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjun","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Qilu Hospital, Shandong University; Innovation Research Center for Sepsis and Multiple Organ Injury, Shandong University","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1186\/s12879-022-07543-8","article-title":"Frequency and mortality of sepsis and septic shock in China: a systematic review and meta-analysis","volume":"22","author":"Liu","year":"2022","journal-title":"BMC Infect Dis"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-024-07694-z","article-title":"Sepsis: key insights, future directions, and immediate goals. 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