{"title":"CD248-targeted BBIR-T cell therapy against late-activated fibroblasts in cardiac repair after myocardial infarction","authors":"Haiting Chen, Ke Hu, Qi Tang, Junzhuo Wang, Qianyu Gu, Jiayu Chen, Jiaxin Hu, Ningxin Peng, Meng Guo, Yaohui Jiang, Qingbo Xu, Jun Xie","doi":"10.1038/s41467-025-56703-2","DOIUrl":null,"url":null,"abstract":"<p>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.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"29 1","pages":""},"PeriodicalIF":14.7000,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Communications","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1038/s41467-025-56703-2","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍：
Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.
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