{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T09:31:03Z","timestamp":1772789463562,"version":"3.50.1"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"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:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sepsis is a life-threatening syndrome caused by a dysregulated host response to infection and remains a major global cause of mortality. Persistent immunosuppression contributes to secondary infections and adverse outcomes, yet the mechanisms underlying late-phase T-cell dysfunction remain incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We integrated publicly available human peripheral blood mononuclear cell single-cell RNA sequencing with a clinically relevant cecal ligation and puncture (CLP) mouse model to characterize CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cell states during sepsis. Key computational findings were supported by flow cytometry and RNA fluorescence\n                      <jats:italic>in situ<\/jats:italic>\n                      hybridization (RNA FISH). The immunophenotypic effects of LAG3 blockade were evaluated in septic mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Single-cell analysis identified a GZMB\n                      <jats:sup>+<\/jats:sup>\n                      CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cell population with an exhaustion-like transcriptional program in sepsis, characterized by increased expression of inhibitory receptors including LAG3 and elevated ZNF683. ZNF683 expression tracked with exhaustion-associated features within the CD8\n                      <jats:sup>+<\/jats:sup>\n                      GZMB\n                      <jats:sup>+<\/jats:sup>\n                      compartment. In CLP mice, anti-LAG3 treatment partially improved frequency of GZMB\n                      <jats:sup>+<\/jats:sup>\n                      CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells by flow cytometry. RNA FISH further showed reduced ZNF683 signals in the lungs and liver of septic mice following LAG3 blockade.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      ZNF683 is associated with an exhaustion-like GZMB\n                      <jats:sup>+<\/jats:sup>\n                      CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell state in sepsis and may contribute to persistent T-cell dysfunction. Further mechanistic studies directly perturbing ZNF683 are needed to determine its causal role and therapeutic potential.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1756339","type":"journal-article","created":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T06:43:37Z","timestamp":1772779417000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The transcription factor ZNF683 marks an exhaustion-like GZMB+CD8+ T cell in sepsis"],"prefix":"10.3389","volume":"17","author":[{"given":"Mingtong","family":"Hou","sequence":"first","affiliation":[{"name":"The Second Clinical Medical School, Lanzhou University","place":["Lanzhou, Gansu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhao","family":"Mi","sequence":"additional","affiliation":[{"name":"The Second Clinical Medical School, Lanzhou University","place":["Lanzhou, Gansu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiyu","family":"Ouyang","sequence":"additional","affiliation":[{"name":"The Second Clinical Medical School, Lanzhou University","place":["Lanzhou, Gansu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenbo","family":"Wang","sequence":"additional","affiliation":[{"name":"Emergency Center, Lanzhou University Second Hospital, Lanzhou University","place":["Lanzhou, Gansu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guiquan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Emergency Center, Lanzhou University Second Hospital, Lanzhou University","place":["Lanzhou, Gansu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shengbao","family":"Wang","sequence":"additional","affiliation":[{"name":"Emergency Center, Lanzhou University Second Hospital, Lanzhou University","place":["Lanzhou, Gansu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.0287","article-title":"The third international consensus definitions for sepsis and septic shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"Jama"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201504-0781OC","article-title":"Assessment of global incidence and mortality of hospital-treated sepsis. 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