Tregs delivered post-myocardial infarction adopt an injury-specific phenotype promoting cardiac repair via macrophages in mice

Alshoubaki, YK; Nayer, B; Lu, YZ; Salimova, E; Lau, SN; Tan, JL; Amann-Zalcenstein, D; Hickey, PF; Del Monte-Nieto, G; Vasanthakumar, A; Martino, MM

Author(s): Alshoubaki, YK; Nayer, B; Lu, YZ; Salimova, E; Lau, SN; Tan, JL; Amann-Zalcenstein, D; Hickey, PF; Del Monte-Nieto, G; Vasanthakumar, A; Martino, MM;
Details: Publication Year 2024-08-01,Volume 15,Issue #1,Page 6480
Journal Title: Nature Communications
Abstract: Regulatory T cells (Tregs) are key immune regulators that have shown promise in enhancing cardiac repair post-MI, although the mechanisms remain elusive. Here, we show that rapidly increasing Treg number in the circulation post-MI via systemic administration of exogenous Tregs improves cardiac function in male mice, by limiting cardiomyocyte death and reducing fibrosis. Mechanistically, exogenous Tregs quickly home to the infarcted heart and adopt an injury-specific transcriptome that mediates repair by modulating monocytes/macrophages. Specially, Tregs lead to a reduction in pro-inflammatory Ly6C(Hi) CCR2(+) monocytes/macrophages accompanied by a rapid shift of macrophages towards a pro-repair phenotype. Additionally, exogenous Treg-derived factors, including nidogen-1 and IL-10, along with a decrease in cardiac CD8(+) T cell number, mediate the reduction of the pro-inflammatory monocyte/macrophage subset in the heart. Supporting the pivotal role of IL-10, exogenous Tregs knocked out for IL-10 lose their pro-repair capabilities. Together, this study highlights the beneficial use of a Treg-based therapeutic approach for cardiac repair with important mechanistic insights that could facilitate the development of novel immunotherapies for MI.
Publisher: Springer Nature
Keywords: Animals; *Myocardial Infarction/immunology/genetics/pathology; *T-Lymphocytes, Regulatory/immunology; *Macrophages/immunology/metabolism; Male; Mice; *Interleukin-10/metabolism/genetics; *Mice, Inbred C57BL; Phenotype; Myocardium/pathology/immunology/metabolism; Monocytes/immunology/metabolism; Myocytes, Cardiac/metabolism/immunology; Fibrosis; CD8-Positive T-Lymphocytes/immunology; Disease Models, Animal; Mice, Knockout
Research Division(s): Advanced Technology And Biology
PubMed ID: 39090108
Publisher's Version: https://doi.org/10.1038/s41467-024-50806-y
Open Access at Publisher's Site: https://doi.org/10.1038/s41467-024-50806-y
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-08-14 09:49:26

Last Modified: 2024-08-14 09:51:50