ATP per molecule of glucose than mitochondrial oxidative phosphorylation, is increasedat a time when expectedly T cells would require more efficient metabolism to meet a large energetic and biosynthetic demands to sustain cell proliferation and cytokine production. The purpose of increased glycolytic activity remains to be fully elucidated, but likely extends beyond that of merely providing ATP or even carbon for biosynthesis, as glucose does not contribute to most of carbon in proliferating T cells [ 12]. It has been proposed that glycolysis may be

In addition to the regulation of T cell activation and tolerance, T cell metabolism has also

compared to regulatory T cells (Tregs), which have increased rates of lipid oxidation [21]. These characteristics do not merely represent metabolic profiles of Teffs versus Tregs, but they actively determine differentiation and polarization. For example, Th17-polarizing

conditions have been shown to induce expression of glycolytic enzymes and to increase

glycolytic activity, while inhibition of glycolysis reciprocally reduces generation of Th17 cells and promotes Treg differentiation [22]. Mechanistically, glycolysis, and likewise

glutaminolysis, may drive Th17 differentiation at least in part by limiting the availability of fructose-6-phosphate to the hexosamine/N-glycan branching pathways, which leads to