Regulatory T cell metabolism at the intersection between autoimmune diseases and cancer

Abstract

Regulatory T cells (Tregs) are critical for peripheral immune tolerance and homeostasis, and altered Treg behavior is involved in many pathologies, including autoimmunity and cancer. The expression of the transcription factor FoxP3 in Tregs is fundamental to maintaining their stability and immunosuppressive function. Recent studies have highlighted the crucial role that metabolic reprogramming plays in controlling Treg plasticity, stability, and function. In this review, we summarize how the availability and use of various nutrients and metabolites influence Treg metabolic pathways and activity. We also discuss how Treg-intrinsic metabolic programs define and shape their differentiation, FoxP3 expression, and suppressive capacity. Lastly, we explore how manipulating the regulation of Treg metabolism might be exploited in different disease settings to achieve novel immunotherapies.