Immune mechanisms in multiple sclerosis: CD3 levels on CD28+ CD4+ T cells link antibody responses to human herpesvirus 6

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine Pub Date : 2025-01-29 DOI:10.1016/j.cyto.2025.156866

Liang Cao , Chen Chen , Wenjun Pi , Yi Zhang , Sara Xue , Voon Wee Yong , Mengzhou Xue

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引用次数: 0

Abstract

Compelling evidence suggests a significant association between antibody-mediated immune responses and multiple sclerosis (MS). However, the exact causal relationships between these immune responses and MS remain unclear. In this study, we conducted a comprehensive examination of the link between antibody-mediated immune responses and MS via Mendelian randomization (MR) analysis to identify specific infectious pathogens potentially involved in the onset and progression of MS. We compared immune cell infiltration between MS patients and control subjects. Furthermore, single-cell sequencing was employed to conduct a comparative analysis of the marker genes associated with each cell subtype between individuals diagnosed with MS and the control cohort. We revealed connections between antibody-mediated immune responses and immune cells, as well as the associations between these immune cells and MS. We discovered that CD3 levels on CD28⁺ CD4⁺ T cells significantly influence MS progression by altering the ratio of human herpesvirus 6 (HHV-6). These findings provide novel insights into the biological mechanisms underlying HHV–6–mediated MS.

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多发性硬化症的免疫机制：CD28+ CD4+ T细胞上的CD3水平与人类疱疹病毒抗体应答有关

令人信服的证据表明，抗体介导的免疫反应与多发性硬化症（MS）之间存在显著关联。然而，这些免疫反应与多发性硬化症之间的确切因果关系尚不清楚。在这项研究中，我们通过孟德尔随机化（MR）分析对抗体介导的免疫反应与MS之间的联系进行了全面的研究，以确定可能参与MS发病和进展的特定感染性病原体，并比较了MS患者和对照组之间的免疫细胞浸润。此外，采用单细胞测序对诊断为MS的个体与对照组之间各细胞亚型相关的标记基因进行比较分析。我们揭示了抗体介导的免疫反应与免疫细胞之间的联系，以及这些免疫细胞与MS之间的联系。我们发现CD28+ CD4+ T细胞上的CD3水平通过改变人疱疹病毒6 （HHV-6）的比例显著影响MS的进展。这些发现为hhv -6介导的MS的生物学机制提供了新的见解。

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

Cytokine 医学-免疫学

CiteScore

7.60

自引率

2.60%

发文量

262

审稿时长

48 days

期刊介绍： The journal Cytokine has an open access mirror journal Cytokine: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. * Devoted exclusively to the study of the molecular biology, genetics, biochemistry, immunology, genome-wide association studies, pathobiology, diagnostic and clinical applications of all known interleukins, hematopoietic factors, growth factors, cytotoxins, interferons, new cytokines, and chemokines, Cytokine provides comprehensive coverage of cytokines and their mechanisms of actions, 12 times a year by publishing original high quality refereed scientific papers from prominent investigators in both the academic and industrial sectors. We will publish 3 major types of manuscripts: 1) Original manuscripts describing research results. 2) Basic and clinical reviews describing cytokine actions and regulation. 3) Short commentaries/perspectives on recently published aspects of cytokines, pathogenesis and clinical results.