T-cell energy metabolism as a controller of cell fate in transplantation

To highlight some of the recent developments in the novel field of immunometabolism and the therapeutic potential of the many regulatory components of this immunometabolic network for transplantation.

In response to cytokines, changes in nutrients, and other alterations in the local milieu, immune cells are capable of changing their internal metabolic pathways to meet their energy demands. Recent studies demonstrate that activated T effectors (Th1 and Th17) are supported by aerobic glycolysis, whereas regulatory T cells and CD8 memory T cells favor fatty acid oxidation and lipid biosynthesis through mitochondrial oxidative phosphorylation. These bioenergetic processes are dependent upon the activation of metabolic sensors such as mammalian target of rapamycin and AMP-activated protein kinase, respectively, indicating that the cross-talk between immunity and metabolism can shape the fate and function of immune cells. Finally, exciting new studies suggest that differences in the bioenergetic mechanisms within the various immune subsets may selectively be exploited for regulating the immune responses.

In this review, we will discuss the metabolic signatures adopted by various immune cells during tolerance versus immunity and the promising avenues that can be modulated by targeting metabolic pathways with either nutrition or pharmacological intervention for establishing long-term transplantation tolerance.