Inhibition of Pyruvate Dehydrogenase Kinase 4 in CD4+ T Cells Ameliorates Intestinal Inflammation
Hoyul Lee, Jae‐Han Jeon, Yujeong Lee, Mi Jin Kim, Woong Kwon, Dipanjan Chanda, Themis Thoudam, Haushabhau S. Pagire, Suvarna H. Pagire, Jin Hee Ahn, Robert A. Harris, Eun Soo Kim, In‐Kyu Lee
Abstract
BACKGROUND & AIMS: T cells, it is uncertain whether the metabolic checkpoint pyruvate dehydrogenase kinase (PDK) in T cells plays a role in the pathogenesis of colitis. METHODS: ). The effect of PDK4 deletion on T-cell activation was also studied in vitro. Furthermore, we examined the effects of a pharmacologic inhibitor of PDK4 on colitis. RESULTS: T cells. Consistent with this, GM-10395, a novel inhibitor of PDK4, suppressed T-cell activation by reducing endoplasmic reticulum-mitochondria calcium transfer, thereby ameliorating murine colitis. CONCLUSIONS: T cells mitigates colitis by metabolic and calcium signaling modulation, suggesting PDK4 as a potential therapeutic target for IBD.