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.