Regulatory T Cells in Atherosclerosis: Is Adoptive Cell Therapy Possible?

SIMPLE SUMMARY: Atherosclerosis is a vascular disease with an asymptomatic debut and development over decades. The mechanisms of progression of atherosclerosis are not completely clear. The development of atherosclerosis involves the infiltration of various types of immune cell subsets into the inner layer of vessel walls, leading to vascular inflammation. These recruited cells mainly have a pro-atherogenic effect. Regulatory T (Treg) cells maintain the balance within the immune system by regulating the activity of these pro-atherogenic immune cells, and they appear to be beneficial in controlling the initiation and progression of atherosclerosis. In particular, Treg cells control anti-inflammatory macrophage polarisation, inhibit foam cell formation, and promote pro-atherogenic Th cell responses through multiple suppressive mechanisms. Here we highlight the most recent advances in our understanding of the roles of Treg cells in the atherogenic process and discuss specific therapeutic strategies for the treatment of atherosclerosis by Treg manipulation. ABSTRACT: Atherosclerosis is an insidious vascular disease with an asymptomatic debut and development over decades. The aetiology and pathogenesis of atherosclerosis are not completely clear. However, chronic inflammation and autoimmune reactions play a significant role in the natural course of atherosclerosis. The pathogenesis of atherosclerosis involves damage to the intima, immune cell recruitment and infiltration of cells such as monocytes/macrophages, neutrophils, and lymphocytes into the inner layer of vessel walls, and the accumulation of lipids, leading to vascular inflammation. The recruited immune cells mainly have a pro-atherogenic effect, whereas CD4(+) regulatory T (Treg) cells are another heterogeneous group of cells with opposite functions that suppress the pathogenic immune responses. Present in low numbers in atherosclerotic plaques, Tregs serve a protective role, maintaining immune homeostasis and tolerance by suppressing pro-inflammatory immune cell subsets. Compelling experimental data suggest that various Treg cell-based approaches may be important in the treatment of atherosclerosis. Here we highlight the most recent advances in our understanding of the roles of FOXP3-expressing CD4(+) Treg cells in the atherogenic process and discuss potential translational strategies for the treatment of atherosclerosis by Treg manipulation.