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Res."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>CD4\u2009+\u2009T cells are major reactive subpopulation for cellular and humoral immune responses following sepsis. The apoptosis of CD4\u2009+\u2009T cells may contribute to sepsis-induced immunosuppression, and preventing the induction of endoplasmic reticulum stress (ERS) can ameliorate apoptosis of CD4\u2009+\u2009T cells in sepsis. The mechanistic target of rapamycin (mTOR) pathway performs an essential regulatory role on ERS-apoptosis of CD4\u2009+\u2009T cells. This study aims to elucidate the underlying mechanisms of mTOR regulation of ERS-apoptosis of CD4\u2009+\u2009T cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, based on the cecal ligation and puncture (CLP) model, 4-phenylbutyric acid (4-PBA), we firstly detected the percentage of ERS-apoptosis of CD4\u2009+\u2009T cells with flow cytometry, Western blotting. Next, we observed the autophagy process and related makers with transmission electron microscopy (TEM) and Western blotting. Furthermore, we created CLP models with T cell-specific mTOR and TSC1 genetic knockout mice, and bafilomycin A1(Baf-A1), a selective inhibitor of autophagy to explore the regulatory role and underlying mechanism of mTOR on ERS-apoptosis of CD4\u2009+\u2009T cells. With rapamycin, we proved the clinical potential of mTOR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Here we observed a considerably higher percentage of apoptotic CD4\u2009+\u2009T cells in sepsis, and 4-PBA (an inhibitor of ERS) could alleviate not only ERS, but also the apoptosis of CD4\u2009+\u2009T cells. As our previous work proved, deletion of mTOR decreased ERS-apoptosis of CD4\u2009+\u2009T cells in sepsis. Furthermore, deficient autophagy, especially impaired autophagic flux was observed in sepsis. Mechanistically, we found knockdown of mTOR erased impaired autophagic flux, decreased ER stress-induced apoptosis, which could be reversed by Baf-A1. More importantly, rapamycin (inhibitor of mTOR) showed great clinical potential.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>we proved that mTOR deletion could alleviate CD4\u2009+\u2009T cells ERS-apoptosis by rescuing autophagy involving autophagosome \u2013lysosome fusion. For the first time, we demonstrate the mTOR-autophagy-ERS-apoptosis axis in sepsis, enriching the targets for future discovery of new sepsis therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00011-025-02114-4","type":"journal-article","created":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T10:21:07Z","timestamp":1770459667000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["mTOR pathway mediates the endoplasmic reticulum stress -apoptosis of CD4+\u2009T cell through inhibiting autophagy flux in sepsis"],"prefix":"10.1007","volume":"75","author":[{"given":"Xianli","family":"Lei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoyu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yawen","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,7]]},"reference":[{"key":"2114_CR1","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","volume":"395","author":"KE Rudd","year":"2020","unstructured":"Rudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, et al. 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