Myocardial-Treg Crosstalk: How to Tame a Wolf

The immune system plays a vital role in maintaining tissue integrity and organismal homeostasis. The sudden stress caused by myocardial infarction (MI) poses a significant challenge for the immune system: it must quickly substitute dead myocardial with fibrotic tissue while controlling overt inflammatory responses. In this review, we will discuss the central role of myocardial regulatory T-cells (Tregs) in orchestrating tissue repair processes and controlling local inflammation in the context of MI. We herein compile recent advances enabled by the use of transgenic mouse models with defined cardiac antigen specificity, explore whole-heart imaging techniques, outline clinical studies and summarize deep-phenotyping conducted by independent labs using single-cell transcriptomics and T-cell repertoire analysis. Furthermore, we point to multiple mechanisms and cell types targeted by Tregs in the infarcted heart, ranging from pro-fibrotic responses in mesenchymal cells to local immune modulation in myeloid and lymphoid lineages. We also discuss how both cardiac-specific and polyclonal Tregs participate in MI repair. In addition, we consider intriguing novel evidence on how the myocardial milieu takes control of potentially auto-aggressive local immune reactions by shaping myosin-specific T-cell development towards a regulatory phenotype. Finally, we examine the potential use of Treg manipulating drugs in the clinic after MI.

Automated summary

The immune system plays a crucial role in maintaining tissue integrity and controlling inflammation during myocardial infarction (MI). This review discusses the central role of regulatory T-cells (Tregs) in tissue repair and inflammation control in the context of MI. It summarizes recent advances in this field, including the use of transgenic mouse models, whole-heart imaging techniques, clinical studies, and single-cell transcriptomics analysis. The review also explores the mechanisms and cell types targeted by Tregs in the infarcted heart and discusses the potential use of Treg manipulating drugs in clinical settings.