{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:10:23Z","timestamp":1788455423180,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,12,15]],"date-time":"2024-12-15T00:00:00Z","timestamp":1734220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["2242022R40060"],"award-info":[{"award-number":["2242022R40060"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The immune system undergoes profound dysregulation in sepsis, characterized by hyperinflammation in the acute phase followed by long\u2010lasting immunosuppression. T\u2010cell exhaustion has been proposed as one facet of sepsis\u2010related immunosuppression, which is characterized by impaired effector function and continuous expression of PD1. However, the current analysis of T\u2010cell exhaustion in the post\u2010sepsis is inadequate. Our current study has identified a progressive increase in the frequency of CD44\n                    <jats:sup>+<\/jats:sup>\n                    CD11a\n                    <jats:sup>+<\/jats:sup>\n                    memory T cells during the post\u2010sepsis phase, accompanied by the upregulation of exhaustion markers (PD\u20101, Lag3, and Tim3) and functional impairments in these cells. TOX is traditionally recognized as a key regulator driving CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell exhaustion in cancer and chronic infection. However, we demonstrate that TOX does not play a critical role in T\u2010cell exhaustion during chronic sepsis but rather is involved in T\u2010cell effector function. Both knockout and \u201cknockdown\u201d of TOX failed to alleviate sepsis\u2010induced T\u2010cell exhaustion. Instead, deletion of TOX impaired the effector function of T cells in chronic sepsis, contradicting its impact on short\u2010term TCR engagement. Our study provides a novel insight into sepsis\u2010induced T\u2010cell exhaustion, highlighting the distinct characteristics of T\u2010cell exhaustion programmed by sepsis.\n                  <\/jats:p>","DOI":"10.1002\/eji.202451395","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T02:18:27Z","timestamp":1734315507000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["TOX Does Not Drive Sepsis\u2010Induced T\u2010Cell Exhaustion"],"prefix":"10.1002","volume":"55","author":[{"given":"Yingyu","family":"Qin","sequence":"first","affiliation":[{"name":"Department of Pathogenic Biology and Immunology Jiangsu Provincial Key Laboratory of Critical Care Medicine School of Medicine Southeast University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilin","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Biology and Immunology Jiangsu Provincial Key Laboratory of Critical Care Medicine School of Medicine Southeast University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengqiu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Biology and Immunology School of Medicine Southeast University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Chen","sequence":"additional","affiliation":[{"name":"The Affiliated Zhongda Hospital Clinical Medical College Southeast University  Nanjing 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