Targeting T cell metabolism to regulate T cell activation, differentiation and function in disease

•Metabolic reprogramming is intimately linked to T cell activation.•Different T cell subsets have different metabolic demands.•Selectivity of targeting metabolism is achieved based on cellular demand.•Targeting metabolism can both inhibit and enhance T cell function.•Targeting metabolism represents a novel means to treat autoimmunity, transplant rejection and enhance immunotherapy.

It is becoming increasingly clear that metabolic reprogramming plays a critical role in T cell activation, differentiation and function. To this end, cellular metabolism not only meets the energetic demands of T cells but also provides critical substrates for their growth and function. Furthermore, metabolites themselves are emerging as key regulators of immune responses. As the details of how metabolic reprogramming regulates immune function are revealed, new potential targets for modulating immune responses have emerged. Indeed, the distinct metabolic demands of different T cell subsets make them exquisitely sensitive to pharmacologic inhibitors of metabolism. In this review, we will describe the emerging strategies whereby targeting metabolism can shape the T cell response.