Engineered immunosuppressive dendritic cells protect against cardiac remodelling PMID: 41951742

RQC and Longevity Regulation

2026-09-03

Engineered immunosuppressive dendritic cells protect against cardiac remodelling

Nature. 2026 May;653(8116):1205-1215. doi: 10.1038/s41586-026-10346-5.

Xiaoying Li ^# ¹ ² ³ ⁴ , Jiamin Li ^# ¹ ⁵ , Guohua Li ^# ¹ ² ³ , Lisheng Zhu ^# ⁶ , Guo Cheng ^# ¹ ⁴ , Huanqiang Li ^# ¹ ² ³ , Hao Lin ¹ ² ³ , Ningqing Jia ¹ ² ³ , Xiaoqian Hong ¹ ² ³ , Ye Liu ¹ , Zhiwei Zhong ¹ , Yize Chen ¹ , Biqing Wang ¹ , Jing Zhao ¹ ² ³ , Zhenqi Hua ¹ ² ³ , Lingjun Wang ¹ ⁴ , Qiming Chen ¹ ² ³ , Peijie Zheng ¹ ² ³ , Shuyuan Sheng ¹ , Songting Gu ¹ , Cheng Ni ¹ , Shuchang Ye ¹ , Changle Ke ¹ , Feimu Zhang ¹ , Mo Li ¹ , Shaohui Shi ⁷ , Junhua He ¹ , Yan Wu ¹ ² ³ , Yinghui Xu ¹ , Minjian Kong ⁸ , Qi Chen ⁹ , Huajun Li ¹ , Yu Zhang ¹ , Jianzhong Sun ¹⁰ , Guanhua Hu ¹ , Chengchen Zhao ¹ , Yiping Dong ¹¹ , Lili Yu ⁶ , Yang Xu ¹² ¹³ ¹⁴ ¹⁵ , Xinyang Hu ¹⁶ ¹⁷ ¹⁸ ¹⁹ ²⁰

Affiliations

1. Department of Cardiology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
2. State Key Laboratory of Transvascular Implantation Devices, Hangzhou, China.
3. Heart Regeneration and Repair Key Laboratory of Zhejiang Province, Hangzhou, China.
4. Binjiang Institute of Zhejiang University, Hangzhou, China.
5. Transvascular Implantation Devices Research Institute, Hangzhou, China.
6. Department of Medical Oncology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
7. Liangzhu Laboratory, Zhejiang University, Hangzhou, China.
8. Department of Cardiothoracic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
9. Department of Anesthesiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
10. Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
11. Department of Ultrasound in Medicine, The Second Affliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
12. Department of Cardiology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. [email protected].
13. State Key Laboratory of Transvascular Implantation Devices, Hangzhou, China. [email protected].
14. Heart Regeneration and Repair Key Laboratory of Zhejiang Province, Hangzhou, China. [email protected].
15. Binjiang Institute of Zhejiang University, Hangzhou, China. [email protected].
16. Department of Cardiology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. [email protected].
17. State Key Laboratory of Transvascular Implantation Devices, Hangzhou, China. [email protected].
18. Heart Regeneration and Repair Key Laboratory of Zhejiang Province, Hangzhou, China. [email protected].
19. Binjiang Institute of Zhejiang University, Hangzhou, China. [email protected].
20. Transvascular Implantation Devices Research Institute, Hangzhou, China. [email protected].
# Contributed equally.

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 function^1-4. 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 lacking^5,6. Dendritic cells (DCs) are key regulators of immune activation and tolerance, providing an opportunity for therapeutic immune reprogramming in cardiac diseases^7,8. 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.