Engineered Regulatory T Lymphocytes Promote Infarcted Heart Repair

作者：Min Zhang, Y. Qin, Ting Zhou, Meilin Liu, T. A. Tang, Ni Xia, Shaofang Nie, Bingjie Lv, Zhengfeng Zhu, Jiao Jiao, Muyang Gu, JingYong Li, Chen Chen, Desheng Hu, Weimin Wang, Li Zhang, Chaolong Wang, Zhilei Shan, X. Cheng · 发表于：Circulation · 年份：2025 · DOI：10.1161/circulationaha.125.076321 · 被引用次数：10 · 研究领域：Cardiac Fibrosis and Remodeling、Peptidase Inhibition and Analysis、Tissue Engineering and Regenerative Medicine

BACKGROUND: Myocardial infarction (MI) initiates a dysregulated healing process characterized by excessive fibrosis and unresolved inflammation, resulting in suboptimal cardiac repair in clinical settings. Regulatory T lymphocytes (Tregs) naturally orchestrate cardiac repair after MI, but their therapeutic potential is limited by inefficient homing to ischemic myocardium. We hypothesize that FAP (fibroblast activation protein)-specific CAR (chimeric antigen receptor) engineering overcomes this barrier by enabling precise delivery of Tregs to FAP⁺-enriched infarct zones, thereby focally amplifying reparative activity within injured myocardium. METHODS: ) donors after infarction. The cardiac outcomes and underlying mechanisms mediated by FCTRs were thoroughly analyzed. Systemic toxicity was evaluated to ensure safety. RESULTS: Intravenous injections of FCTRs on day 3 after injury led to targeted engraftment in the damaged cardiac tissue. Compared with controls treated with vehicle or mock Tregs, mice receiving FCTRs exhibited remarkable cardiac functional recovery in both MI and ischemia-reperfusion models by day 14, accompanied by reduced fibrosis and decreased inflammation, all achieved without compromising the integrity of cardiac tissue. Absence of IL-10 in the engineered CAR Tregs abrogated their therapeutic efficacy, whereas the ablation of Areg showed no functional impairment. We further demonstrated that the beneficial effects of FCTRs depended on IL-10 production, whic...