The endoplasmic reticulum stress status of CD4+ T lymphocytes and its association with mTOR-mediated autophagic-lysosomal disorder in elderly sepsis patients

Aimsto clarify the endoplasmic reticulum stress (ERS) status of CD4+ T lymphocytes in sepsis patients, particularly elderly individuals aged over 65 years, and to elucidate its association with mTOR-mediated autophagic-lysosomal disorder.Methods62 sepsis patients were enrolled from January 1 to July...

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Main Authors: Wei Cheng, Jiahui Zhang, Dongkai Li, Yawen Xie, Xianli Lei, Hao Wang, Na Cui
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1648075/full
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author Wei Cheng
Jiahui Zhang
Dongkai Li
Yawen Xie
Xianli Lei
Hao Wang
Na Cui
author_facet Wei Cheng
Jiahui Zhang
Dongkai Li
Yawen Xie
Xianli Lei
Hao Wang
Na Cui
author_sort Wei Cheng
collection DOAJ
description Aimsto clarify the endoplasmic reticulum stress (ERS) status of CD4+ T lymphocytes in sepsis patients, particularly elderly individuals aged over 65 years, and to elucidate its association with mTOR-mediated autophagic-lysosomal disorder.Methods62 sepsis patients were enrolled from January 1 to July 31, 2024. Peripheral blood mononuclear cells (PBMCs) were isolated within 24 hours post-enrollment. flow cytometry was used to quantify the expression levels of ERS markers (CHOP and GRP78) and mTOR-mediated autophagic-lysosomal fusion markers (mTOR, LC3II and P62) on CD4+ T lymphocytes. These markers were compared between sepsis and non-sepsis patients, elderly and non-elderly sepsis patients, survivors and non-survivors based on in-hospital mortality. The correlations between CHOP mean fluorescence intensity (MFI) and CD4+ T lymphocyte count, LC3II MFI, and P62 MFI were also analyzed.ResultsCompared to non-septic controls, sepsis patients exhibited significantly higher CHOP and GRP78 MFIs (210.9 versus 142.9, P<0.001 and 279.1 versus 223.7, P=0.045). Within the sepsis group, elderly patients and non-survivors showed significantly higher CHOP and GRP78 MFIs (334.4 versus 164.2, P<0.001 and 374.3 versus 218.6, P<0.001; 390.8 versus 177.6, P<0.001 and 389.1 versus 227.0, P<0.001). CHOP MFI on CD4+ T lymphocytes showed significant correlations with LC3II and P62 MFIs in sepsis patients (Pearson’s correlation r=0.657, p<0.001 and r=0.811, P<0.001), elderly sepsis patients (r=0.644, P<0.001 and r=0.710, P<0.001), and non-survived elderly sepsis patients (r=0.897, P<0.001 and r=0.772, P=0.009).ConclusionERS in CD4+ T cells was enhanced in sepsis patients, particularly in elderly and non-survived individuals; ERS is strongly associated with mTOR-mediated autophagic-lysosomal disorder.Clinical trial registrationchictr.org.cn, identifier ChiCTR2300074175.
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spelling doaj-art-ec887947d7ef42c6bf7bac2cd231aa5b2025-08-26T04:13:09ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-08-011610.3389/fimmu.2025.16480751648075The endoplasmic reticulum stress status of CD4+ T lymphocytes and its association with mTOR-mediated autophagic-lysosomal disorder in elderly sepsis patientsWei Cheng0Jiahui Zhang1Dongkai Li2Yawen Xie3Xianli Lei4Hao Wang5Na Cui6Department of Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, ChinaDepartment of Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, ChinaDepartment of Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, ChinaDepartment of Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, ChinaDepartment of Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, ChinaDepartment of Critical Care Medicine, Beijing Jishuitan Hospital, Capital Medical University, Beijing, ChinaDepartment of Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, ChinaAimsto clarify the endoplasmic reticulum stress (ERS) status of CD4+ T lymphocytes in sepsis patients, particularly elderly individuals aged over 65 years, and to elucidate its association with mTOR-mediated autophagic-lysosomal disorder.Methods62 sepsis patients were enrolled from January 1 to July 31, 2024. Peripheral blood mononuclear cells (PBMCs) were isolated within 24 hours post-enrollment. flow cytometry was used to quantify the expression levels of ERS markers (CHOP and GRP78) and mTOR-mediated autophagic-lysosomal fusion markers (mTOR, LC3II and P62) on CD4+ T lymphocytes. These markers were compared between sepsis and non-sepsis patients, elderly and non-elderly sepsis patients, survivors and non-survivors based on in-hospital mortality. The correlations between CHOP mean fluorescence intensity (MFI) and CD4+ T lymphocyte count, LC3II MFI, and P62 MFI were also analyzed.ResultsCompared to non-septic controls, sepsis patients exhibited significantly higher CHOP and GRP78 MFIs (210.9 versus 142.9, P<0.001 and 279.1 versus 223.7, P=0.045). Within the sepsis group, elderly patients and non-survivors showed significantly higher CHOP and GRP78 MFIs (334.4 versus 164.2, P<0.001 and 374.3 versus 218.6, P<0.001; 390.8 versus 177.6, P<0.001 and 389.1 versus 227.0, P<0.001). CHOP MFI on CD4+ T lymphocytes showed significant correlations with LC3II and P62 MFIs in sepsis patients (Pearson’s correlation r=0.657, p<0.001 and r=0.811, P<0.001), elderly sepsis patients (r=0.644, P<0.001 and r=0.710, P<0.001), and non-survived elderly sepsis patients (r=0.897, P<0.001 and r=0.772, P=0.009).ConclusionERS in CD4+ T cells was enhanced in sepsis patients, particularly in elderly and non-survived individuals; ERS is strongly associated with mTOR-mediated autophagic-lysosomal disorder.Clinical trial registrationchictr.org.cn, identifier ChiCTR2300074175.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1648075/fullendoplasmic reticulum stresssepsiselderlymTORautophagiclysosomal disorder
spellingShingle Wei Cheng
Jiahui Zhang
Dongkai Li
Yawen Xie
Xianli Lei
Hao Wang
Na Cui
The endoplasmic reticulum stress status of CD4+ T lymphocytes and its association with mTOR-mediated autophagic-lysosomal disorder in elderly sepsis patients
Frontiers in Immunology
endoplasmic reticulum stress
sepsis
elderly
mTOR
autophagiclysosomal disorder
title The endoplasmic reticulum stress status of CD4+ T lymphocytes and its association with mTOR-mediated autophagic-lysosomal disorder in elderly sepsis patients
title_full The endoplasmic reticulum stress status of CD4+ T lymphocytes and its association with mTOR-mediated autophagic-lysosomal disorder in elderly sepsis patients
title_fullStr The endoplasmic reticulum stress status of CD4+ T lymphocytes and its association with mTOR-mediated autophagic-lysosomal disorder in elderly sepsis patients
title_full_unstemmed The endoplasmic reticulum stress status of CD4+ T lymphocytes and its association with mTOR-mediated autophagic-lysosomal disorder in elderly sepsis patients
title_short The endoplasmic reticulum stress status of CD4+ T lymphocytes and its association with mTOR-mediated autophagic-lysosomal disorder in elderly sepsis patients
title_sort endoplasmic reticulum stress status of cd4 t lymphocytes and its association with mtor mediated autophagic lysosomal disorder in elderly sepsis patients
topic endoplasmic reticulum stress
sepsis
elderly
mTOR
autophagiclysosomal disorder
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1648075/full
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