Sugars and fat - A healthy way to generate functional regulatory T cells.

Cellular metabolism has emerged as an important regulator of adaptive immunity. While the metabolic requirements of conventional T cells are increasingly understood, the role of cellular metabolism in Foxp3+ regulatory T (Treg) cells is less clear. Although it is well accepted that repression of Akt/mTOR, HIF-1α and aerobic glycolysis are important for the efficient generation of Treg cells in vitro, clear evidence how these pathways impact on Treg-cell development in vivo is limited. Furthermore, newer studies have shown that the same pathways that appear to suppress Treg-cell development are active in and required for functionally mature Treg cells. Thus, it becomes increasingly evident that development and function of regulatory T cells require different wiring of metabolic pathways. Finally, it is likely that critical differences remain to be uncovered between the metabolism of resting or 'naïve' Treg cells and those fully differentiated and actively engaged in suppression. In this comment, we briefly discuss our current understanding of Treg-cell metabolism and the need to address this area with new approaches based on in vivo models.