Matched and mismatched metabolic fuels in lymphocyte function

Immunological function requires metabolic support to suit the needs of lymphocytes at a variety of distinct differentiation and activation states. It is now evident that the signaling pathways that drive lymphocyte survival and activity can directly control cellular metabolism. This linkage provides a mechanism by which activation and specific signaling pathways provide a supply of appropriate and required nutrients to support cell functions in a pro-active supply rather than consumption-based metabolic model. In this way, the metabolism and fuel choices of lymphocytes are guided to specifically match the anticipated needs. If the fuel choice or metabolic pathways of lymphocytes are dysregulated, however, metabolic checkpoints can become activated to disrupt immunological function. These changes are now shown in several immunological diseases and may open new opportunities to selectively enhance or suppress specific immune functions through targeting of glucose, lipid, or amino acid metabolism.

► Lymphocytes balance glucose, lipid, and amino acid metabolism for energy and growth.
► Metabolic fuel choices are controlled by activation and differentiation signals.
► Distinct lymphocyte subsets and types have specific metabolic programs.
► Targeting metabolism can initiate checkpoints to stop growth or to kill cells.
► Metabolic approaches to direct lymphocyte fate will be useful in immune disease.