Immunometabolism crosstalk between regulatory T cells and glucose homeostasis of type 1 diabetes.

Type 1 diabetes mellitus (T1D) is an autoimmune disease that is associated with the loss of pancreatic β cells. Regulatory T cells (Tregs) play a critical role in the maintenance of immune tolerance; however, the number and function of Tregs have been found to be compromised in T1D. Genetic changes in FOXP3, as well as the role of hyperglycaemia and the accumulation of advanced glycation end products, have been proposed as potential mechanisms for the dysfunction of Tregs. However, the current understanding suggests that the role of the metabolic reprogramming associated with hyperglycaemia is more likely to be a potential mechanism for the instability of Tregs rather than a well-established primary mechanism for the development of T1D. Several therapeutic strategies have been explored in experimental models for the management of autoimmune diseases associated with Tregs dysfunction. These include the administration of low-dose interleukin-2, metformin, and dietary or microbiome-based therapies. These therapies have been found to modulate the immune system; however, the efficacy of these therapies for the management of T1D is to be established. In the present review article, the current understanding of the role of the interrelationship between hyperglycaemia, metabolic reprogramming, and Tregs-mediated immune tolerance in the pathogenesis of type 1 diabetes is reviewed.