Regulatory T (Treg) cells have been shown to have anti-atherogenic functions, protecting against atherosclerosis development and progression. A new study now shows that Treg cells also influence atherosclerosis regression by promoting the resolution of plaque inflammation through the suppression of macrophage and T cell pro-inflammatory responses and the induction of a pro-resolving macrophage phenotype that facilitates tissue repair and plaque regression.

Kathryn Moore and colleagues show that Treg cell numbers increase within regressing plaques in multiple mouse models of atherosclerosis regression. Single-cell RNAsequencing analyses revealed that the Treg cell profile changes during atherosclerotic plaque regression induced by lipid lowering, indicating that Treg cells from regressing plaques derive from peripheral differentiation of naive T cells, whereas Treg cells from progressing plaques derive from the thymus, and have increased activation and metabolic activity. The researchers also demonstrate that Treg cells are required for atherosclerosis regression. Antibody-mediated depletion of Treg cells in mice blocked the atherosclerosis regression achieved with aggressive lipid-lowering therapy. Atherosclerotic plaques from mice depleted of Treg cells had an inflammatory phenotype similar to that of progressing plaques and did not show hallmarks of inflammation resolution. The findings indicated that Treg cells were required for pro-resolving processes during atherosclerosis regression, including decreased T helper 1 cell response, increased macrophage emigration, polarization of macrophages to an M2-like tissue-reparative phenotype, clearance of dying cells and stimulation of the production of and response to lipid mediators of inflammation resolution.

Together, these findings suggest that therapeutic expansion of Treg cells, combined with lipid-lowering therapy, might be a promising approach to promote inflammation resolution and atherosclerosis regression.