Chen Haiting, Hu Ke, Tang Qi, Wang Junzhuo, Gu Qianyu, Chen Jiayu, Hu Jiaxin, Peng Ningxin, Guo Meng, Jiang Yaohui, Xu Qingbo, Xie Jun
Department of Cardiology, National Cardiovascular Disease Regional Center for Anhui, the First Affiliated Hospital of Anhui Medical University, No.218 Jixi Road, Hefei, Anhui, 230022, China.
Affiliated Drum Tower Hospital, Medical School, Nanjing University, No.321 Zhongshan Road, Nanjing, Jiangsu, 210008, China.
Nat Commun. 2025 Mar 27;16(1):2895. doi: 10.1038/s41467-025-56703-2.
Excessive cardiac fibrosis is a key cause of heart failure and adverse ventricular remodeling after myocardial infarction. The abnormally activated fibroblasts after scar maturation are the chief culprit. Single-cell RNA sequencing of mouse cardiac interstitial cells after myocardial infarction depicts a late-activated fibroblast subpopulation F-Act and initially identifies its characteristic antigen CD248, which is also verified in human hearts. On this basis, we develop a CD248-targeted biotin-binding immune receptor T cell therapy against F-Act to correct cardiac repair disorders. In our study, the precise removal of F-Act after the scar matured effectively inhibits fibrotic expansion in the peri-infarct zone and improves cardiac function. This therapy provides an idea for the treatment of cardiac fibrosis and also promotes the application of engineered T cells to non-tumor diseases.
过度的心脏纤维化是心肌梗死后心力衰竭和不良心室重构的关键原因。瘢痕成熟后异常激活的成纤维细胞是主要罪魁祸首。对小鼠心肌梗死后心脏间质细胞进行单细胞RNA测序，描绘出一个晚期激活的成纤维细胞亚群F-Act，并初步鉴定出其特征性抗原CD248，这在人类心脏中也得到了验证。在此基础上，我们开发了一种针对F-Act的靶向CD248的生物素结合免疫受体T细胞疗法，以纠正心脏修复紊乱。在我们的研究中，瘢痕成熟后精确清除F-Act可有效抑制梗死周边区的纤维化扩展并改善心脏功能。该疗法为心脏纤维化的治疗提供了思路，也推动了工程化T细胞在非肿瘤疾病中的应用。
