New insights about regulatory T cells distribution and function with exercise: the role of immunometabolism.

A lack of physical activity is linked to the development of many chronic diseases through a chronic low-grade inflammation state. It is now well accepted that the immune system plays a central role in the development of several chronic cardiometabolic diseases, including insulin resistance, type 2 diabetes, atherosclerosis, heart failure and certain types of cancer. Exercise elicits a strong anti-inflammatory response independently of weight loss and can be a useful non-pharmacologic strategy to counteract the low-grade inflammation. The CD4+CD25+CD127-FoxP3+ Regulatory T (Treg) cells are a unique subset of helper T-cells, which regulate immune response and establish self-tolerance through the secretion of immunoregulatory cytokines, such as IL-10 and TGF-β, and the suppression of the function and activity of many immune effector cells (including monocytes/macrophages, dendritic cells, CD4+ and CD8+ T cells, and Natural Killers). The metabolic phenotype of Tregs are regulated by the transcription factor Foxp3, providing to these cells flexibility in fuel choice, but preference to increased fatty acid oxidation. In this Review, we focus on the mechanisms by which exercise - both acute and chronic - exerts its anti-inflammatory effects through Treg cells mobilization. Furthermore, we discuss the implications of immunometabolic changes during exercise for the modulation of Treg immunosuppressive function. Along the review, we will discuss: a) the role of intensity on acute exercise-induced Treg cell mobilization and regulatory cytokine secretion through metabolic changes; b) the impact of exercise training on Treg cells function using studies with rodent models; c) the link between cardiorespiratory fitness and Treg cells in chronic exercised humans; d) longitudinal human evidence regarding the role of exercise training on Treg cells phenotype. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.