Pharmacological activation of pyruvate kinase M2 (PKM2) inhibits CD4+ T cell pathogenicity and suppresses autoimmunity

Pyruvate kinase (PK) catalyzes the conversion of phosphoenolpyruvate to pyruvate during glycolysis. The PK isoform PKM2 has additional roles in regulation of gene transcription and protein phosphorylation. PKM2 controls macrophage metabolic remodeling in inflammation, but its role in T cell biology is poorly understood. These results show that TEPP-46, an activator of PKM2, reduces CD4+ T cell activation, proliferation, and cytokine production by inhibiting essential signaling pathways and preventing glycolysis. RNA-Seq was performed on resting or activated CD4+ T cells treated with or without the PKM2 activator TEPP-46.