調節(jié)性 T 細胞（Tregs）是關鍵的免疫調節(jié)劑，已顯示出在增強心肌梗死后心臟修復方面的潛力模式，盡管其機制仍然難以捉摸搖籃。在這里長期間，我們表明學習，通過全身給藥外源性Tregs在MI后循環(huán)中迅速增加Treg數量覆蓋範圍，通過限制心肌細胞死亡和減少纖維化來改善雄性小鼠的心臟功能能力建設。從機制上講的方法，外源性 Tregs 迅速返回梗死心臟不難發現，并采用損傷特異性轉錄組貢獻法治，通過調節(jié)單核細胞/巨噬細胞介導修復。特別是發展需要，Tregs 導致促炎 Ly6CHi CCR2+ 單核細胞/巨噬細胞減少攻堅克難，同時巨噬細胞迅速向促修復表型轉變。此外顯示，外源性 Treg 衍生因子（包括 nidogen-1 和 IL-10）以及心臟 CD8+ T 細胞數量的減少介導心臟中促炎單核細胞/巨噬細胞亞群的減少雙向互動。支持 IL-10 的關鍵作用，被 IL-10 敲除的外源性 Tregs 失去了其促修復能力設計能力∑放?？傊@項研究強調了基于 Treg 的治療方法在心臟修復中的有益用途求得平衡，具有重要的機制見解紮實做，可以促進心肌梗死新型免疫療法的開發(fā)，Tregs通過巨噬細胞促進心梗損傷恢復至關重要。

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..

論文信息：

論文題目：Tregs delivered post-myocardial infarction adopt an injury-specific phenotype promoting cardiac repair via macrophages in mice

期刊名稱： nature communications

時間期卷：15, Article number: 6480 (2024)pages685–700 (2024)

在線時間：2024年8月1日

研究亮點：

- 全身給藥外源性Tregs可促進心肌梗死后的心臟修復

- 外源性Tregs是缺血性心肌的歸巢提供深度撮合服務，并表達損傷特異性轉錄組

- 外源性Tregs的促修復效果取決于Mo/MΦ

- Mo/MΦ 響應外源性 Tregs 獲得促修復基因表達譜

- 心肌梗死后 Tregs 的缺失導致心臟 Mo/MΦ 出現(xiàn)促炎表型

- Tregs 通過 Ly6C+ CCR2+ Mo/MΦ 亞群減輕其影響