mTORC1 signaling is crucial for regulatory T cells to suppress macrophage-mediated inflammatory response after acute myocardial infarction.

Post-infarction inflammatory response results in worse remodeling and dysfunction following myocardial infarction (MI). Supression of post-infarction inflammation would be a logical approach of alleviating post-infarction injury and promoting cardiac repair. In this study, we investigated the significance of mTORC1 signaling in the anti-inflammatory activity of regulatory T cells (Tregs) after MI. Using the murine MI model with wild type and Rag1(-/-) mice, we found that the mechanistic target of rapamycin compex 1 (mTORC1) signaling was upregulated in Tregs infiltrating into the infarcted myocardium, rather than in circulating Tregs after MI. The anti-inflammatory activity of infiltrating Tregs was significantly stronger than that of circulating Tregs. This was demonstrated by a higher expression of anti-inflammatory cytokines in the infiltrating Tregs and a robust suppression of proinflammatory cytokine production by macrophages. In an adoptive transfer analysis, compared with normal splenic Tregs, rapamycin-treated splenic Tregs ineffectively suppressed the post-infarction inflammatory response of infiltrating macrophages. In addition, in vitro cultured primary cardiomyocytes treated with mild oxygen glucose deprivation induced mTORC1 activation and a higher anti-inflammatory activity of Tregs in a coculture assay. Our study identified a new mechanism by which infiltrating Tregs subdue post-infarction inflammation. Understanding and utilizing this information would be helpful for designing new therapeutic interventions for MI.