CD248-targeted BBIR-T cell therapy against late-activated fibroblasts in cardiac repair after myocardial infarction
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 infarc...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-03-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56703-2 |
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| author | Haiting Chen Ke Hu Qi Tang Junzhuo Wang Qianyu Gu Jiayu Chen Jiaxin Hu Ningxin Peng Meng Guo Yaohui Jiang Qingbo Xu Jun Xie |
| author_facet | Haiting Chen Ke Hu Qi Tang Junzhuo Wang Qianyu Gu Jiayu Chen Jiaxin Hu Ningxin Peng Meng Guo Yaohui Jiang Qingbo Xu Jun Xie |
| author_sort | Haiting Chen |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-b7fd28e657c2454cb9672252cd27caed |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-b7fd28e657c2454cb9672252cd27caed2025-08-20T03:41:14ZengNature PortfolioNature Communications2041-17232025-03-0116111610.1038/s41467-025-56703-2CD248-targeted BBIR-T cell therapy against late-activated fibroblasts in cardiac repair after myocardial infarctionHaiting Chen0Ke Hu1Qi Tang2Junzhuo Wang3Qianyu Gu4Jiayu Chen5Jiaxin Hu6Ningxin Peng7Meng Guo8Yaohui Jiang9Qingbo Xu10Jun Xie11Department of Cardiology, National Cardiovascular Disease Regional Center for Anhui, the First Affiliated Hospital of Anhui Medical University, No.218 Jixi RoadDepartment of Cardiology, National Cardiovascular Disease Regional Center for Anhui, the First Affiliated Hospital of Anhui Medical University, No.218 Jixi RoadNHC Key Laboratory of Antibody Technique, Nanjing Medical University, No.101 Longmian RoadAffiliated Drum Tower Hospital, Medical School, Nanjing University, No.321 Zhongshan RoadAffiliated Drum Tower Hospital, Medical School, Nanjing University, No.321 Zhongshan RoadDepartment of Cardiology, National Cardiovascular Disease Regional Center for Anhui, the First Affiliated Hospital of Anhui Medical University, No.218 Jixi RoadCardiovascular Disease Center, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi Clinical College of Wuhan University, No.158 Wuyang RoadDepartment of Cardiology, National Cardiovascular Disease Regional Center for Anhui, the First Affiliated Hospital of Anhui Medical University, No.218 Jixi RoadAffiliated Drum Tower Hospital, Medical School, Nanjing University, No.321 Zhongshan RoadAffiliated Drum Tower Hospital, Medical School, Nanjing University, No.321 Zhongshan RoadDepartment of Cardiology, the First Affiliated Hospital, Zhejiang University School of Medicine, No.79 Qingchun RoadDepartment of Cardiology, National Cardiovascular Disease Regional Center for Anhui, the First Affiliated Hospital of Anhui Medical University, No.218 Jixi RoadAbstract 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.https://doi.org/10.1038/s41467-025-56703-2 |
| spellingShingle | Haiting Chen Ke Hu Qi Tang Junzhuo Wang Qianyu Gu Jiayu Chen Jiaxin Hu Ningxin Peng Meng Guo Yaohui Jiang Qingbo Xu Jun Xie CD248-targeted BBIR-T cell therapy against late-activated fibroblasts in cardiac repair after myocardial infarction Nature Communications |
| title | CD248-targeted BBIR-T cell therapy against late-activated fibroblasts in cardiac repair after myocardial infarction |
| title_full | CD248-targeted BBIR-T cell therapy against late-activated fibroblasts in cardiac repair after myocardial infarction |
| title_fullStr | CD248-targeted BBIR-T cell therapy against late-activated fibroblasts in cardiac repair after myocardial infarction |
| title_full_unstemmed | CD248-targeted BBIR-T cell therapy against late-activated fibroblasts in cardiac repair after myocardial infarction |
| title_short | CD248-targeted BBIR-T cell therapy against late-activated fibroblasts in cardiac repair after myocardial infarction |
| title_sort | cd248 targeted bbir t cell therapy against late activated fibroblasts in cardiac repair after myocardial infarction |
| url | https://doi.org/10.1038/s41467-025-56703-2 |
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