{"title":"TIM1+ Breg细胞在心肌缺血再灌注损伤中的作用。","authors":"Cong Zeng, Jianchuan Qi, Feifei Wu, Weijun Yang, Minjian Kong, Haifeng Cheng, Aiqiang Dong, Jie Han, Wei Chen, Dajin Chen, Qunjun Duan","doi":"10.1038/s41420-025-02725-0","DOIUrl":null,"url":null,"abstract":"<p><p>Recent studies found that treatment with an anti-T-cell immunoglobulin mucin-1 (TIM1) monoclonal antibody (RMT1-10) regulated immune responses by inducing regulatory B cells (Bregs). However, the role of these cells in myocardial ischemia-reperfusion injury (IRI) is unknown. This study aimed to investigate the protective effect of RMT1-10 on myocardial IRI and its potential mechanism. We established a myocardial IRI model, and Triphenyl tetrazolium chloride staining, Terminal deoxynucleotidyl transferase nick-end-labeling, hematoxylin and eosin, and transmission electron microscopy were performed to examine the myocardial infarction size, myocardial cell apoptosis, and cardiomyocyte morphology and structure. The data showed that RMT1-10 could alleviate myocardial IRI, increase the number of TIM1<sup>+</sup>Bregs and interleukin 10 (IL-10) secretion, and regulate the expression of inflammatory factors after myocardial IRI. However, treatment with RMT1-10 and Anti-CD20 abrogated the protective effect of RMT-10. In addition, RMT1-10 treatment inhibited T cells but significantly activated Tregs after IRI, while RMT1-10 combined with Anti-CD20 abolished this effect on Tregs. Furthermore, sequencing analysis showed marked expression changes among genes related to several classical signaling pathways in response to RMT1-10. Taken together, these findings indicated that RMT1-10 could increase the number of TIM1<sup>+</sup> Bregs and regulate IL-10-mediated inflammatory reactions, activate Tregs to inhibit inflammation, and might regulate the above-mentioned signaling pathways to protect against myocardial IRI.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"453"},"PeriodicalIF":7.0000,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12504465/pdf/","citationCount":"0","resultStr":"{\"title\":\"The effect of TIM1<sup>+</sup> Breg cells in myocardial ischemia-reperfusion injury.\",\"authors\":\"Cong Zeng, Jianchuan Qi, Feifei Wu, Weijun Yang, Minjian Kong, Haifeng Cheng, Aiqiang Dong, Jie Han, Wei Chen, Dajin Chen, Qunjun Duan\",\"doi\":\"10.1038/s41420-025-02725-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Recent studies found that treatment with an anti-T-cell immunoglobulin mucin-1 (TIM1) monoclonal antibody (RMT1-10) regulated immune responses by inducing regulatory B cells (Bregs). However, the role of these cells in myocardial ischemia-reperfusion injury (IRI) is unknown. This study aimed to investigate the protective effect of RMT1-10 on myocardial IRI and its potential mechanism. We established a myocardial IRI model, and Triphenyl tetrazolium chloride staining, Terminal deoxynucleotidyl transferase nick-end-labeling, hematoxylin and eosin, and transmission electron microscopy were performed to examine the myocardial infarction size, myocardial cell apoptosis, and cardiomyocyte morphology and structure. The data showed that RMT1-10 could alleviate myocardial IRI, increase the number of TIM1<sup>+</sup>Bregs and interleukin 10 (IL-10) secretion, and regulate the expression of inflammatory factors after myocardial IRI. However, treatment with RMT1-10 and Anti-CD20 abrogated the protective effect of RMT-10. In addition, RMT1-10 treatment inhibited T cells but significantly activated Tregs after IRI, while RMT1-10 combined with Anti-CD20 abolished this effect on Tregs. Furthermore, sequencing analysis showed marked expression changes among genes related to several classical signaling pathways in response to RMT1-10. Taken together, these findings indicated that RMT1-10 could increase the number of TIM1<sup>+</sup> Bregs and regulate IL-10-mediated inflammatory reactions, activate Tregs to inhibit inflammation, and might regulate the above-mentioned signaling pathways to protect against myocardial IRI.</p>\",\"PeriodicalId\":9735,\"journal\":{\"name\":\"Cell Death Discovery\",\"volume\":\"11 1\",\"pages\":\"453\"},\"PeriodicalIF\":7.0000,\"publicationDate\":\"2025-10-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12504465/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell Death Discovery\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41420-025-02725-0\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Death Discovery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41420-025-02725-0","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
The effect of TIM1+ Breg cells in myocardial ischemia-reperfusion injury.
Recent studies found that treatment with an anti-T-cell immunoglobulin mucin-1 (TIM1) monoclonal antibody (RMT1-10) regulated immune responses by inducing regulatory B cells (Bregs). However, the role of these cells in myocardial ischemia-reperfusion injury (IRI) is unknown. This study aimed to investigate the protective effect of RMT1-10 on myocardial IRI and its potential mechanism. We established a myocardial IRI model, and Triphenyl tetrazolium chloride staining, Terminal deoxynucleotidyl transferase nick-end-labeling, hematoxylin and eosin, and transmission electron microscopy were performed to examine the myocardial infarction size, myocardial cell apoptosis, and cardiomyocyte morphology and structure. The data showed that RMT1-10 could alleviate myocardial IRI, increase the number of TIM1+Bregs and interleukin 10 (IL-10) secretion, and regulate the expression of inflammatory factors after myocardial IRI. However, treatment with RMT1-10 and Anti-CD20 abrogated the protective effect of RMT-10. In addition, RMT1-10 treatment inhibited T cells but significantly activated Tregs after IRI, while RMT1-10 combined with Anti-CD20 abolished this effect on Tregs. Furthermore, sequencing analysis showed marked expression changes among genes related to several classical signaling pathways in response to RMT1-10. Taken together, these findings indicated that RMT1-10 could increase the number of TIM1+ Bregs and regulate IL-10-mediated inflammatory reactions, activate Tregs to inhibit inflammation, and might regulate the above-mentioned signaling pathways to protect against myocardial IRI.
期刊介绍：
Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary.
Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.
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