脓毒症中失调的免疫反应：来自调节性T细胞相关基因表达的见解

Dysregulated Immune Responses in Sepsis: Insights From Treg-Related Gene Expression.

作者信息

Zhu Guangyan, Liao Yanlin, Liu Simin, Liu Ping, Yang Kai, Tan Minghe, Yi Lisha, Zhang Dingyu, Xia Haifa

机构信息

Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.

Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.

出版信息

J Inflamm Res. 2025 Aug 27;18:11689-11702. doi: 10.2147/JIR.S523019. eCollection 2025.

INTRODUCTION

Sepsis, a life-threatening dysregulated immune response to infection, has a high global mortality rate. Tregs play dual roles in sepsis pathogenesis, with their expansion linked to immunosuppression. This study explores Treg dynamics and the novel role of CD82 in sepsis.

METHODS

Peripheral blood from sepsis patients was analyzed using scRNA-seq. Machine learning (SVM, LASSO, random forest) integrated scRNA-seq data with three GEO datasets (n=380) to identify biomarkers. CD82 expression in Tregs was validated via flow cytometry and RT-qPCR in CLP mouse model. Anti-CD25 antibody depleted Tregs in mice.

RESULTS

The scRNA-seq revealed neutrophil expansion and T/NK cell reduction in sepsis. Tregs were enriched and exhibited CD82 upregulation. A seven-gene diagnostic signature (CD82, CD52, EVI2B, IL32, RCAN3, AQP3, NAP1L1) achieved high accuracy (AUCs up to 99.9%). Treg-depleted CLP mice showed reduced CD82 expression, elevated IL-6 and neutrophils, and worsened inflammation, implicating CD82 in immune modulation.

DISCUSSION

CD82 may mediate Treg hyperactivation during sepsis, balancing the immune response and suppression. The gene signature shows diagnostic potential, but CD82's mechanistic role needs further investigation. Therapeutic targeting of CD82 could improve sepsis management.

引言

脓毒症是一种对感染的危及生命的免疫反应失调，全球死亡率很高。调节性T细胞（Tregs）在脓毒症发病机制中发挥双重作用，其扩增与免疫抑制有关。本研究探讨了Tregs的动态变化以及CD82在脓毒症中的新作用。

方法

使用单细胞RNA测序（scRNA-seq）分析脓毒症患者的外周血。机器学习（支持向量机、套索回归、随机森林）将scRNA-seq数据与三个基因表达综合数据库（GEO）数据集（n = 380）整合，以识别生物标志物。通过流式细胞术和逆转录定量聚合酶链反应（RT-qPCR）在盲肠结扎穿孔（CLP）小鼠模型中验证Tregs中CD82的表达。抗CD25抗体清除小鼠体内的Tregs。

结果

scRNA-seq显示脓毒症中中性粒细胞扩增和T细胞/自然杀伤细胞（T/NK细胞）减少。Tregs富集并表现出CD82上调。一个七基因诊断标志物（CD82、CD52、EVI2B、IL32、RCAN3、AQP3、NAP1L1）具有很高的准确性（曲线下面积高达99.9%）。Tregs耗竭的CLP小鼠显示CD82表达降低、白细胞介素-6（IL-6）和中性粒细胞升高，炎症恶化，表明CD82参与免疫调节。