Regulatory T cells in ischemic cardiovascular injury and repair

Ischemic injury triggers a heightened inflammatory response that is essential for tissue repair, but excessive and chronic inflammatory responses contribute to the pathogenesis of ischemic cardiovascular disease. Regulatory T cells (Tregs), a major regulator of self-tolerance and immune suppression, control innate and adaptive immune responses, modulate specific immune cell subsets, prevent excessive inflammation, and participate in tissue repair after ischemia. Herein, we summarize the multiple potential mechanisms by which Tregs exert suppressor functions including modulation of cytokine production, alteration of cell-cell interactions, and disruption of metabolic pathways. Furthermore, we review the role of Tregs implicated in ischemic injury and repair including myocardial, limb, and cerebral ischemia. We conclude with a perspective on the therapeutic opportunities and future challenges of Treg biology in understanding the pathogenesis of ischemic cardiovascular disease states. •Tregs attenuate atherosclerotic development and plaque vulnerability.•Tregs improve acute ischemic myocardial injury, whereas dysfunctional and pro-inflammatory Tregs promote adverse cardiac remodeling in ischemic cardiomyopathy and chronic heart failure.•In a few non-cardiac ischemic injury models, Tregs were found to have stage-specific antithetical effects (promoting) tissue injury.•Clinical studies are underway incorporating the use of Treg-based therapies for myocardial infarction and chronic inflammatory disease states.•Emerging small molecule and biologic-based therapeutics targeting Tregs hold promise for a range of ischemic cardiovascular disease states.