Herpesvirus entry mediator on effector memory CD8+ T cells mediates the effects of sterol ester (27:1/18:1) levels on critical sepsis

IF 3.2 4区医学 Q3 IMMUNOLOGY

Immunology letters Pub Date : 2026-02-01 Epub Date: 2025-10-12 DOI:10.1016/j.imlet.2025.107103

Junpu Cai , Haitao Li , Wenqiang Cui , Mingyu Hou , Huaiqian Bo , Ning Zhang , Yifan Wang , Jingwen Zhu , Caijun Tian

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引用次数: 0

Abstract

Background

Lipid metabolism is closely associated with the development of sepsis; however, the relationship between specific lipid molecules and sepsis remains unclear, as does the extent to which immune cell traits mediate the effects of lipid levels on critical sepsis.

Objective

The effects of lipids on critical sepsis were examined in this work, along with the potential mediating function of immune cell characteristics in this process, using Mendelian randomization.

Materials and Methods

A comprehensive two-sample Mendelian randomization analysis was conducted using genetic data from a genome-wide association study of 179 lipids, a large-scale genome-wide association study of 731 immune cell traits, and the latest genome-wide association study of critical sepsis. The ratios of immune cell trait indirect and mediating effects were computed using the coefficient product approach.

Results

We identified 4 lipids and 18 immune cell traits that had a negative causal relationship with critical sepsis, and 1 lipid and 13 immune cell traits that had a positive causal relationship with critical sepsis. Herpesvirus entry mediator (HVEM) on effector memory CD8+ T cells mediates the effects of sterol ester (27:1/18:1) levels on critical sepsis, accounting for 6.1% of this effect.

Conclusion

Our study confirmed the genetic causal relationship between lipids, immune cell traits, and critical sepsis, highlighting the potential mediating role of HVEM on effector memory CD8+ T cells and providing insights that may aid in the development of strategies for the prevention and treatment of critical sepsis in the clinic.

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效应记忆CD8+ T细胞的疱疹病毒进入介质介导甾醇酯（27:1/18:1）水平对严重败血症的影响

背景：脂质代谢与脓毒症的发生密切相关；然而，特异性脂质分子与脓毒症之间的关系尚不清楚，免疫细胞特性在多大程度上介导脂质水平对重症脓毒症的影响也不清楚。目的：本研究采用孟德尔随机化方法，探讨脂质对重症脓毒症的影响，以及免疫细胞特性在这一过程中的潜在介导作用。材料和方法：利用179种脂质全基因组关联研究、731种免疫细胞性状的大规模全基因组关联研究和最新的危重性脓毒症全基因组关联研究的遗传数据，进行全面的双样本孟德尔随机化分析。采用系数积法计算免疫细胞性状间接效应和中介效应的比值。结果：我们确定了4种脂质和18种免疫细胞特征与临界败血症具有负相关的因果关系，1种脂质和13种免疫细胞特征与临界败血症具有正相关的因果关系。效应记忆CD8+ T细胞上的疱疹病毒进入介质（HVEM）介导甾醇酯（27:1/18:1）水平对严重败血症的影响，占该效应的6.1%。结论：我们的研究证实了脂质、免疫细胞特性和重症脓毒症之间的遗传因果关系，突出了HVEM对效应记忆CD8+ T细胞的潜在介导作用，并为临床预防和治疗重症脓毒症的策略的制定提供了新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Immunology letters 医学-免疫学

CiteScore

7.60

自引率

0.00%

发文量

审稿时长

44 days

期刊介绍： Immunology Letters provides a vehicle for the speedy publication of experimental papers, (mini)Reviews and Letters to the Editor addressing all aspects of molecular and cellular immunology. The essential criteria for publication will be clarity, experimental soundness and novelty. Results contradictory to current accepted thinking or ideas divergent from actual dogmas will be considered for publication provided that they are based on solid experimental findings. Preference will be given to papers of immediate importance to other investigators, either by their experimental data, new ideas or new methodology. Scientific correspondence to the Editor-in-Chief related to the published papers may also be accepted provided that they are short and scientifically relevant to the papers mentioned, in order to provide a continuing forum for discussion.