A pyridine derivative metabolite 4-Hydroxypyridine induces metabolic reprogramming and enhances NK cell function 4590

Description Pyridine derivatives, such as pyridoxine (vitamin B6), nicotinic acid (Niacin, vitamin B3) have significant effects on immune cells, including modulation of their metabolic pathways. Previously, we reported that 4-hydroxypyridine enhances memory NK cell expansion and regulates IFN-γ production. In this study, we further explore the effects of 4-hydroxypyridine on human NK cells. Treatment of NK cells with 4-hydroxypyridine resulted in increased expression of LAMP-1 and granzyme A, key markers of NK cell activation and cytotoxicity. Proliferation assays demonstrated that 4-hydroxypyridine significantly promotes NK cell proliferation. Additionally, cytotoxicity assays revealed that NK cells cultured in the presence of 4-hydroxypyridine exhibit enhanced killing of target K562 cells. Notably, the effect of 4-hydroxypyridine persisted for over 120 hours, suggesting long-lasting alterations in NK cell functionality. Transcriptomic analysis revealed that 4-hydroxypyridine treatment led to significant upregulation of amino acid metabolic pathways, including phenylalanine and tyrosine metabolism, as well as glycine, serine, and threonine metabolism. Moreover, 4-hydroxypyridine significantly upregulated the expression of EFNA2, FOXR1 and TXNIP. These findings suggest that 4-hydroxypyridine can induce metabolic reprogramming and enhances NK cell function. Further studies are ongoing to elucidate the signaling pathways involved in the metabolic reprogramming induced by 4-hydroxypyridine.