Pyruvate kinase M2-deficiency in T cells leads to exacerbation of ConA hepatitis and alterations of T cell polarization

In autoimmune liver disease, impaired homeostasis results from a dysbalance between regulatory T cells (Tregs) and T effector cells (Teff). Activated Teff cells undergo metabolic re-programming to preferential aerobic glycolysis known as Warburg Effect. Aerobic glycolysis is required for T cell growth and effector function. Contrary, Tregs rely on fatty acid oxidation. The Warburg effect and glycolytic switch are promoted by dimerization of pyruvate kinase M2 that acts as a cofactor for HIF-1a to induce transcription of inflammatory cytokines and glycolytic enzymes. These effects can be counterbalanced by allosteric tetramerization the PKM2. The cytosolic PKM2 tetramer has high enzymatic activity and ensures an intact glycolytic flux.