調(diào)節(jié)性 T 細(xì)胞（Tregs）是關(guān)鍵的免疫調(diào)節(jié)劑喜愛，已顯示出在增強(qiáng)心肌梗死后心臟修復(fù)方面的潛力的發生，盡管其機(jī)制仍然難以捉摸配套設備。在這里處理，我們表明明確了方向，通過全身給藥外源性Tregs在MI后循環(huán)中迅速增加Treg數(shù)量發展空間，通過限制心肌細(xì)胞死亡和減少纖維化來改善雄性小鼠的心臟功能研究與應用。從機(jī)制上講效高化，外源性 Tregs 迅速返回梗死心臟初步建立，并采用損傷特異性轉(zhuǎn)錄組綜合運用，通過調(diào)節(jié)單核細(xì)胞/巨噬細(xì)胞介導(dǎo)修復(fù)。特別是的方法，Tregs 導(dǎo)致促炎 Ly6CHi CCR2+ 單核細(xì)胞/巨噬細(xì)胞減少實事求是，同時巨噬細(xì)胞迅速向促修復(fù)表型轉(zhuǎn)變。此外落到實處，外源性 Treg 衍生因子（包括 nidogen-1 和 IL-10）以及心臟 CD8+ T 細(xì)胞數(shù)量的減少介導(dǎo)心臟中促炎單核細(xì)胞/巨噬細(xì)胞亞群的減少服務水平。支持 IL-10 的關(guān)鍵作用，被 IL-10 敲除的外源性 Tregs 失去了其促修復(fù)能力技術創新√幚矸椒?？傊@項(xiàng)研究強(qiáng)調(diào)了基于 Treg 的治療方法在心臟修復(fù)中的有益用途持續向好，具有重要的機(jī)制見解關規定，可以促進(jìn)心肌梗死新型免疫療法的開發(fā)，Tregs通過巨噬細(xì)胞促進(jìn)心梗損傷恢復(fù)兩個角度入手。

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(diǎn)：

- 全身給藥外源性Tregs可促進(jìn)心肌梗死后的心臟修復(fù)

- 外源性Tregs是缺血性心肌的歸巢安全鏈，并表達(dá)損傷特異性轉(zhuǎn)錄組

- 外源性Tregs的促修復(fù)效果取決于Mo/MΦ

- Mo/MΦ 響應(yīng)外源性 Tregs 獲得促修復(fù)基因表達(dá)譜

- 心肌梗死后 Tregs 的缺失導(dǎo)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