Pyruvate dehydrogenase phosphatase catalytic subunit 2 limits Th17 differentiation

Significance Th17 cells favor glycolytic metabolism. Pyruvate dehydrogenase, which facilitates entry into the oxidative phosphorylation circle, is inhibited by pyruvate dehydrogenase phosphatase catalytic subunit 2 (PDP2). Our studies demonstrate that the transcription factor ICER/CREM, which is known to promote Th17 differentiation and related pathology, suppresses the expression of PDP2 and diverts energy production into the glycolytic pathway. In lupus-prone mice and people with systemic lupus erythematosus, PDP2 levels are decreased and its replenishment suppresses Th17 differentiation.