中文摘要：

调节性 T 细胞 （Tregs） 是关键的免疫调节剂，已显示出在增强心肌梗死后心脏修复方面的潜力，尽管其机制仍然难以捉摸。在这里，我们表明，通过全身给药外源性Tregs在MI后循环中迅速增加Treg数量，通过限制心肌细胞死亡和减少纤维化来改善雄性小鼠的心脏功能。从机制上讲，外源性 Tregs 迅速返回梗死心脏，并采用损伤特异性转录组，通过调节单核细胞/巨噬细胞介导修复。特别是，Tregs 导致促炎 Ly6CHi CCR2+ 单核细胞/巨噬细胞减少，同时巨噬细胞迅速向促修复表型转变。此外，外源性 Treg 衍生因子（包括 nidogen-1 和 IL-10）以及心脏 CD8+ T 细胞数量的减少介导心脏中促炎单核细胞/巨噬细胞亚群的减少。支持 IL-10 的关键作用，被 IL-10 敲除的外源性 Tregs 失去了其促修复能力。总之，这项研究强调了基于 Treg 的治疗方法在心脏修复中的有益用途，具有重要的机制见解，可以促进心肌梗死新型免疫疗法的开发，Tregs通过巨噬细胞促进心梗损伤恢复。

英文摘要：

Regulatory T cells (Tregs) are key immune regulators that have shown promise in enhancing cardiac repair post-MI, although the mechanisms remain elusive. Here, we show that rapidly increasing Treg number in the circulation post-MI via systemic administration of exogenous Tregs improves cardiac function in male mice, by limiting cardiomyocyte death and reducing fibrosis. Mechanistically, exogenous Tregs quickly home to the infarcted heart and adopt an injury-specific transcriptome that mediates repair by modulating monocytes/macrophages. Specially, Tregs lead to a reduction in pro-inflammatory Ly6CHi CCR2+ monocytes/macrophages accompanied by a rapid shift of macrophages towards a pro-repair phenotype. Additionally, exogenous Treg-derived factors, including nidogen-1 and IL-10, along with a decrease in cardiac CD8+ T cell number, mediate the reduction of the pro-inflammatory monocyte/macrophage subset in the heart. Supporting the pivotal role of IL-10, exogenous Tregs knocked out for IL-10 lose their pro-repair capabilities. Together, this study highlights the beneficial use of a Treg-based therapeutic approach for cardiac repair with important mechanistic insights that could facilitate the development of novel immunotherapies for MI..

论文信息：

论文题目：Tregs delivered post-myocardial infarction adopt an injury-specific phenotype promoting cardiac repair via macrophages in mice

期刊名称： nature communications

时间期卷：15, Article number: 6480 (2024)pages685–700 (2024)

在线时间：2024年8月1日

研究亮点：

- 全身给药外源性Tregs可促进心肌梗死后的心脏修复

- 外源性Tregs是缺血性心肌的归巢，并表达损伤特异性转录组

- 外源性Tregs的促修复效果取决于Mo/MΦ

- Mo/MΦ 响应外源性 Tregs 获得促修复基因表达谱

- 心肌梗死后 Tregs 的缺失导致心脏 Mo/MΦ 出现促炎表型

- Tregs 通过 Ly6C+ CCR2+ Mo/MΦ 亚群减轻其影响

材料方法：