老年脓毒症患者CD4+ T淋巴细胞内质网应激状态及其与mTOR介导的自噬-溶酶体紊乱的关系
The endoplasmic reticulum stress status of CD4+ T lymphocytes and its association with mTOR-mediated autophagic-lysosomal disorder in elderly sepsis patients.
作者信息
Cheng Wei, Zhang Jiahui, Li Dongkai, Xie Yawen, Lei Xianli, Wang Hao, Cui Na
机构信息
Department 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, China.
Department of Critical Care Medicine, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China.
出版信息
Front Immunol. 2025 Aug 26;16:1648075. doi: 10.3389/fimmu.2025.1648075. eCollection 2025.
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 non-survived elderly sepsis patients (r=0.897, P<0.001 and r=0.772, P=0.009).
CONCLUSION
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.
CLINICAL TRIAL REGISTRATION
chictr.org.cn, identifier ChiCTR2300074175.
目的
明确脓毒症患者，尤其是65岁以上老年患者CD4+ T淋巴细胞的内质网应激（ERS）状态，并阐明其与mTOR介导的自噬溶酶体功能障碍的关联。
方法
选取2024年1月1日至7月31日期间的62例脓毒症患者。入院后24小时内分离外周血单个核细胞（PBMC）。采用流式细胞术定量检测CD4+ T淋巴细胞上ERS标志物（CHOP和GRP78）以及mTOR介导的自噬溶酶体融合标志物（mTOR、LC3II和P62）的表达水平。基于住院死亡率，比较脓毒症患者与非脓毒症患者、老年与非老年脓毒症患者、存活者与非存活者之间的这些标志物。还分析了CHOP平均荧光强度（MFI）与CD4+ T淋巴细胞计数、LC3II MFI和P62 MFI之间的相关性。
结果
与非脓毒症对照组相比，脓毒症患者的CHOP和GRP78 MFI显著更高（分别为210.9对142.9，P<0.001；279.1对223.7，P=0.045）。在脓毒症组中，老年患者和非存活者的CHOP和GRP78 MFI显著更高（分别为334.4对164.2，P<0.001；374.3对218.6，P<0.001；390.8对177.6，P<0.001；389.1对227.0，P<0.001）。脓毒症患者、老年脓毒症患者以及未存活的老年脓毒症患者中，CD4+ T淋巴细胞上的CHOP MFI与LC3II和P62 MFI均呈显著相关性（Pearson相关系数r分别为0.657，P<0.001；0.811，P<0.001；0.644，P<0.001；0.710，P<0.001；0.897，P<0.001；0.772，P=0.009）。
结论
脓毒症患者，尤其是老年和未存活个体，CD4+ T细胞中的ERS增强；ERS与mTOR介导的自噬溶酶体功能障碍密切相关。
临床试验注册
chictr.org.cn，标识符ChiCTR2300074175
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