Metabolic control of regulatory T cell development and function

• Nutrients, vitamins, and hormones control the generation and homeostasis of Tregs.
• Microbiota-derived metabolites impact upon intestinal Treg accumulation and function.
• mTOR and metabolic programming orchestrate Treg differentiation and activity.
• Tregs are crucial in maintaining host metabolic balance and microbiota diversity.

Foxp3+ regulatory T cells (Tregs) maintain immune tolerance and play an important role in immunological diseases and cancers. Recent studies have revealed an intricate relationship between Treg biology and host and microbial metabolism. Various metabolites or nutrients produced by host and commensal microbes, such as vitamins and short-chain fatty acids (SCFAs), regulate Treg generation, trafficking, and function. Furthermore, cell intrinsic metabolic programs, orchestrated by mTOR and other metabolic sensors, modulate Foxp3 induction and Treg suppressive activity. Conversely, Tregs are crucial in regulating obesity-associated inflammation and host metabolic balance, and in shaping homeostasis of gut microbiota. We review here the interplay between Tregs and metabolism, with a particular focus on how host, commensal, and cellular metabolism impinge upon Treg homeostasis and function.