CLINICAL TRIAL article
Front. Immunol.
Sec. Inflammation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1648075
The Endoplasmic Reticulum Stress Status of CD4+ T lymphocytes and Its Association with mTOR-mediated Autophagic-lysosomal Disorder in Elderly Sepsis Patients
Provisionally accepted
- 1Peking Union Medical College Hospital State Key Laboratory of Complex Severe and Rare Diseases, Dongcheng, China
- 2Beijing Jishuitan Hospital Affiliated to Capital Medical University, Beijing, China
- 3Beijing Chaoyang Hospital Affiliated to Capital Medical University, Beijing, China
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Aims: to 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.Methods: 62 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.Results: Compared 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 nonsurvived elderly sepsis patients (r=0.897, P<0.001 and r=0.772, P=0.009).ERS 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.
Keywords: Endoplasmic Reticulum Stress, Sepsis, Elderly, mTOR, Autophagiclysosomal disorder
Received: 16 Jun 2025; Accepted: 07 Aug 2025.
Copyright: © 2025 Cheng, Zhang, Li, Xie, Lei, Wang and Cui. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Na Cui, Beijing Chaoyang Hospital Affiliated to Capital Medical University, Beijing, China
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