Pharmacological Activation of Pyruvate Kinase M2 Inhibits CD4⁺ T Cell Pathogenicity and Suppresses Autoimmunity.

ABSTRACT: 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 has been shown to control macrophage metabolic remodeling in inflammation, but its role in T cell biology is poorly understood. Here, we report PKM2 upregulation, phosphorylation, and nuclear accumulation in murine and human CD4⁺ T cells following activation in vitro. Treatment of T cells with TEPP-46, an allosteric activator that induces PKM2 tetramerization and blocks its nuclear translocation, strongly reduces their activation, proliferation, and cytokine production by inhibiting essential signaling pathways and thus preventing the engagement of glycolysis. TEPP-46 lim

SUBMITTER: Angiari S 

PROVIDER: S-EPMC7001035 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature