工程免疫抑制树突状细胞防止心脏重塑

工程免疫抑制树突状细胞防止心脏重塑

作者： 小柯机器人 发布时间：2026/4/9 14:50:46

本期文章：《自然》：Online/在线发表

工程免疫抑制树突状细胞防止心脏重塑，这一成果由浙江大学胡新央小组经过不懈努力而取得。相关论文于2026年4月8日发表在《自然》杂志上。

本研究表明，工程化的免疫抑制和纤维化靶向DCs（iCDCs）可有效防止病理性心脏重构。在缺血再灌注损伤、心肌梗死和压力过载的无主题模型中，iCDC治疗可减轻炎症性心脏纤维化，改善心脏灌注并保持收缩力。在机制上，iCDC通过直接抑制免疫和基质细胞激活或间接促进调节性T细胞克隆扩增来提供持续的心脏保护。重要的是，在非人类灵长类动物心肌梗死模型中，iCDC治疗还可以减少心脏纤维化，改善心脏功能和收缩功能，而不会引起全身毒性。这些发现确立了病灶靶向免疫调节作为控制心脏纤维化的可行策略，并确定工程树突状细胞作为治疗心脏重构和心力衰竭的有前途的治疗平台。

据介绍，心力衰竭仍然是发病率和死亡率的主要原因，但目前还没有批准的治疗方法能有效预防或逆转病理性心脏纤维化和相关的心功能下降。慢性炎症是缺血或血流动力学应激后病理性纤维化的主要驱动因素，但缺乏局部重新平衡损伤和修复性免疫反应而不全身免疫抑制的策略。树突状细胞（DCs）是免疫激活和耐受性的关键调节因子，为心脏疾病的治疗性免疫重编程提供了机会。

附：英文原文

Title: Engineered immunosuppressive dendritic cells protect against cardiac remodelling

Author: Li, Xiaoying, Li, Jiamin, Li, Guohua, Zhu, Lisheng, Cheng, Guo, Li, Huanqiang, Lin, Hao, Jia, Ningqing, Hong, Xiaoqian, Liu, Ye, Zhong, Zhiwei, Chen, Yize, Wang, Biqing, Zhao, Jing, Hua, Zhenqi, Wang, Lingjun, Chen, Qiming, Zheng, Peijie, Sheng, Shuyuan, Gu, Songting, Ni, Cheng, Ye, Shuchang, Ke, Changle, Zhang, Feimu, Li, Mo, Shi, Shaohui, He, Junhua, Wu, Yan, Xu, Yinghui, Kong, Minjian, Chen, Qi, Li, Huajun, Zhang, Yu, Sun, Jianzhong, Hu, Guanhua, Zhao, Chengchen, Dong, Yiping, Yu, Lili, Xu, Yang, Hu, Xinyang

Issue&Volume: 2026-04-08

Abstract: Heart failure remains a leading cause of morbidity and mortality, yet no approved therapies effectively prevent or reverse pathological cardiac fibrosis and the associated decline in cardiac function1,2,3,4. Chronic inflammation is a central driver of pathological fibrosis after ischaemic or haemodynamic stress, but strategies that locally rebalance injurious and reparative immune responses without systemic immunosuppression are lacking5,6. Dendritic cells (DCs) are key regulators of immune activation and tolerance, providing an opportunity for therapeutic immune reprogramming in cardiac diseases7,8. Here we show that engineered immunosuppressive and fibrosis-targeted DCs (iCDCs) effectively protect against pathological cardiac remodelling. In mouse models of ischaemia–reperfusion injury, myocardial infarction and pressure overload, iCDC therapy reduced inflammatory cardiac fibrosis, improved cardiac perfusion and preserved contractility. Mechanistically, iCDCs conferred sustained cardioprotection directly by suppressing immune and stromal cell activation or indirectly through promoting clonal expansion of regulatory T cells. Importantly, in a non-human primate model of myocardial infarction, iCDC therapy also reduced cardiac fibrosis, improved cardiac perfusion and contractile function without inducing systemic toxicity. These findings establish lesion-targeted immune modulation as a feasible strategy to control cardiac fibrosis and identify engineered dendritic cells as a promising therapeutic platform for treating cardiac remodelling and heart failure.

DOI: 10.1038/s41586-026-10346-5

Source: https://www.nature.com/articles/s41586-026-10346-5

主题：树突状细胞