Cellular Metabolism Controls Lymphocyte Activation and Differentiation

Upon antigen recognition, activated lymphocytes differentiate into different subsets depending on the cytokine environment. It is clear that in addition to the signaling and transcriptional reprogramming that governs lymphocyte activation, metabolic reprogramming plays an essential role in the activation and differentiation process. While naïve T cells utilize glucose oxidation through the TCA cycle, activated lymphocytes engage mainly in aerobic glycolysis, a phenomenon that has been long observed in tumor cells. While effector T cells show a higher glycolytic rate, memory T cells and also regulatory T cells show higher dependence on fatty acid oxidation. To this end, several molecules and enzymes critical for regulating metabolism have also emerged as playing an important role in guiding both T cell differentiation and function. Understanding how metabolism regulates different T cell subsets provides a new avenue by which to therapeutically regulate immune-mediated diseases.