CCR5-Mediated Reprogramming of Regulatory T Cells and Monocytic-Myeloid-Derived Suppressor Cells in Young Dyslipidemic Individuals: A Plausible Therapeutic Approach

IF 5 3区医学 Q2 IMMUNOLOGY

Immunology Pub Date : 2025-05-19 DOI:10.1111/imm.13941

Komal Sagar, Shamima Akhtar, Nikita Kumar, Anil Kumar Tomar, Ambuj Roy, Milind P. Hote, Sudheer Arava, Savita Yadav, Alpana Sharma

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引用次数: 0

Abstract

Chemokine receptor CCR5 is upregulated in the regulatory T cells (Tregs) and monocytic-myeloid-derived suppressor cells (M-MDSCs) of young dyslipidemic individuals. In this study, we investigated the role of CCR5 in regulating the phenotypic and functional plasticity of Tregs and M-MDSCs during the preclinical phase of atherosclerosis. Inflammatory conditions induce a phenotypic shift in Tregs and M-MDSCs, characterised by enhanced expression of CCR5 and pro-inflammatory cytokines. Tregs from dyslipidemic (DLP) and coronary artery disease (CAD) patients exhibited a mixed Th1/Th17/Treg phenotype, whilst M-MDSCs displayed elevated markers of activation and inflammation. CCR5 inhibition via DAPTA (10⁻⁸ M) restored the immune suppressive phenotype and function of Tregs and M-MDSCs in vitro. Migration of dysfunctional Tregs and M-MDSCs to CCL5 stimulus was also reduced after DAPTA treatment in vitro. In vivo, DAPTA reduced IL-12 expression and elevated IL-10 expression in Tregs and M-MDSCs. Therapeutically targeting CCR5 in Tregs and M-MDSCs of young naive dyslipidemic individuals aids in the dampening of early inflammation and can prevent the progression of atherosclerosis.

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ccr5介导的调节性T细胞和单核髓源性抑制细胞重编程：一种可行的治疗方法

趋化因子受体CCR5在年轻血脂异常个体的调节性T细胞（Tregs）和单核髓源性抑制细胞（M-MDSCs）中上调。在这项研究中，我们研究了CCR5在动脉粥样硬化临床前阶段调节Tregs和M-MDSCs表型和功能可塑性中的作用。炎症条件诱导treg和M-MDSCs的表型变化，其特征是CCR5和促炎细胞因子的表达增强。来自血脂异常（DLP）和冠状动脉疾病（CAD）患者的Treg表现出混合的Th1/Th17/Treg表型，而M-MDSCs表现出升高的激活和炎症标志物。通过DAPTA （10-8 M）抑制CCR5在体外恢复Tregs和M- mdscs的免疫抑制表型和功能。DAPTA体外治疗后，功能失调的Tregs和M-MDSCs向CCL5刺激的迁移也减少。在体内，DAPTA降低了Tregs和M-MDSCs中IL-12的表达，升高了IL-10的表达。在年轻幼稚的血脂异常个体的treg和M-MDSCs中靶向治疗CCR5有助于抑制早期炎症，并可以防止动脉粥样硬化的进展。

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 医学-免疫学

CiteScore

11.90

自引率

1.60%

发文量

175

审稿时长

4-8 weeks

期刊介绍： Immunology is one of the longest-established immunology journals and is recognised as one of the leading journals in its field. We have global representation in authors, editors and reviewers. Immunology publishes papers describing original findings in all areas of cellular and molecular immunology. High-quality original articles describing mechanistic insights into fundamental aspects of the immune system are welcome. Topics of interest to the journal include: immune cell development, cancer immunology, systems immunology/omics and informatics, inflammation, immunometabolism, immunology of infection, microbiota and immunity, mucosal immunology, and neuroimmunology. The journal also publishes commissioned review articles on subjects of topical interest to immunologists, and commissions in-depth review series: themed sets of review articles which take a 360° view of select topics at the heart of immunological research.