Xia N, Lu Y, Gu M, et al. - To clarify the existence, unique phenotype as well as role of so-called tissue regulatory T cells (Tregs) in the heart, researchers performed this study wherein they monitored dynamic accumulation of Tregs in the injured myocardium, using mouse models of myocardial infarction (MI), myocardial ischemia/reperfusion injury (I/R injury) or cardiac cryoinjury. In the myocardium of these models, Tregs were highly enriched. By transcriptomic data, Tregs isolated from the injured hearts were shown to have plenty of differentially expressed transcripts vs their lymphoid counterparts including heart draining lymphoid nodes, with a phenotype of encouraging infarct repair, suggesting a unique feature. An important role of interleukin (IL)-33/ST2 axis was evident for sustaining heart Treg populations. A critical role of Sparc (secreted acidic cysteine rich glycoprotein) (which was highly expressed by heart Tregs) in protecting the heart against MI, by raising collagen content and boosting maturation in the infarct zone, was revealed. In this study, a phenotypically as well as a functionally unique population of heart Tregs was unveiled and characterized, which may set the base to harness Tregs for cardioprotection in MI and other cardiac disorders.