Abstract 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. Funding Sources Supported by Tulane University start-up grant. Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)
Tiwari et al. (Sat,) studied this question.