Navigating T-Cell Immunometabolism in Transplantation

Recently, a new discipline termed "immunometabolism" has transformed the field of immunology. It encompasses the study of the intrinsic metabolic pathways of different immune subsets and their impact on cellular fate and function. For instance, broadly speaking, proinflammatory cells depend on glycolysis and glutamine oxidation, whereas cells involved in anti-inflammatory response, such as Foxp3+ regulatory T (Treg) cells, use predominantly fatty acid oxidation. However, although a useful paradigm, this actually is a reductionist view, and the engagement of these metabolic pathways is not mutually exclusive between these subsets. Over the past several years, new insights and new methods to better dissect, define, and harness the metabolic properties of immune cells for immunotherapeutic purposes have come to the forefront. In this review, we will discuss the metabolic heterogeneity of different T-cell subsets as well as basic principles of integrative technologies, such as metabolomics, which can be used to better understand the metabolic signatures of immune responses. Given the interest of exploiting this information in the context of transplantation, we will highlight the scope of immunometabolism in unraveling novel mechanisms of immune regulation that can be manipulated to promote Treg cell stability and function while inhibiting T effectors to establish long-term transplantation tolerance.