2019 ATVB Plenary Lecture: Interleukin-2 Therapy in Cardiovascular Disease: The Potential to Regulate Innate and Adaptive Immunity.

Regulatory T cells and type-2 innate lymphoid cells represent 2 subsets of immune cells, which have been shown in preclinical models to be important in atherosclerosis and myocardial repair. Regulatory T cells play a crucial role in immune homeostasis and tolerance via their interactions with effector T cells, dendritic cells, and monocytes/macrophages. They also utilize and secrete inhibitory cytokines, including interleukin 10 and transforming growth factor β, to regulate or suppress pathogenic immune responses. Type-2 innate lymphoid cells have an important role in type-2 immune responses and tissue repair through secreting interleukins 5 and 13, as well as a variety of biological mediators and growth factors. Intriguingly, interleukin-2 has emerged as a common cytokine, which can be harnessed to upregulate both cell types, and also has important translational consequences as clinical trials are ongoing for its use in cardiovascular disease. Here, we briefly review the biology of these regulatory immune cell types, discuss the preclinical and clinical evidence for their functions in cardiovascular disease, examine the prospects for clinical translation and current ongoing trials, and finally, postulate how overlap in the mechanisms of upregulation may be leveraged in future treatments for patients.