{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T20:29:37Z","timestamp":1793737777283,"version":"4.6.1"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T00:00:00Z","timestamp":1785024000000},"content-version":"vor","delay-in-days":25,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["115115"],"award-info":[{"award-number":["115115"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Sepsis is a life-threatening systemic inflammation marked by an initial hyperinflammatory phase. Tregs are pivotal in tempering this early immune response. Semaphorins, originally neuronal guidance cues, have emerged as immune modulators. Notably, Sema3E influences dendritic cell and T cell responses, but its role in Treg-mediated regulation during endotoxemia is unclear. WT and Sema3e\u2212\/\u2212 mice were subjected to LPS-induced endotoxemia. Treg frequencies, proliferation and migration were assessed by flow cytometry and Transwell assays, respectively. Serum cytokines (eg IL-10) were quantified using ELISA. A TNFRSF25 agonist was administered to expand Tregs in vivo, and adoptive transfers of WT or Sema3e\u2212\/\u2212 Tregs were performed. Clinical scores and survival were recorded. Sema3e\u2212\/\u2212 mice exhibited significantly impaired Treg expansion and proliferation, altered migratory patterns with reduced Treg accumulation in spleen and lymph nodes, and consequently lower serum cytokine levels (eg IFN-\u03b3) compared to WT, correlating with exacerbated disease severity. DR3-mediated Treg expansion in Sema3e\u2212\/\u2212 mice did not improve their clinical outcomes. Furthermore, adoptively transferred Sema3e\u2212\/\u2212 Tregs failed to confer protection in endotoxemic recipients, unlike WT Tregs. Sema3E is essential for optimal Treg responses and immune regulation during severe LPS-induced inflammation. Its absence compromises Treg expansion, localization, and function, worsening sepsis outcomes. These findings highlight Sema3E as a critical component of Treg-mediated immunosuppression and a potential therapeutic target for improving immune homeostasis in sepsis.<\/jats:p>","DOI":"10.1093\/immhor\/vlag031","type":"journal-article","created":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T14:44:53Z","timestamp":1785077093000},"source":"Crossref","is-referenced-by-count":0,"title":["Semaphorin 3E regulates the response of regulatory T cells to lipopolysaccharide-induced systemic inflammation"],"prefix":"10.1093","volume":"10","author":[{"given":"Sina","family":"Taefehshokr","sequence":"first","affiliation":[{"name":"Department of Immunology, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba , Winnipeg, Manitoba,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ifeoma","family":"Okwor","sequence":"additional","affiliation":[{"name":"Department of Immunology, Rady Faculty of Health Sciences, Max Rady College 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