Epigenetic Modulation by Lactylation in Sepsis: Linking Metabolism to Immune Dysfunction
Yinghong Chen, Haoyuan Hu, Congwei Wang, Junxuan Wu, Jie Zan, Yuntao Liu
Abstract
Lactate, traditionally viewed as a metabolic byproduct, is now recognized as a key regulator of immune and epigenetic processes in sepsis. A recently discovered post-translational modification, lactylation, utilizes lactate as a substrate and plays a crucial role in cellular regulation. Accumulating evidence suggests that elevated lactate levels contribute to immune dysfunction in sepsis by modulating the activity of various immune cells. This modification links metabolic changes to immune regulation, making it a crucial factor in sepsis progression. Understanding how lactylation is altered in sepsis unveils critical links between immunometabolism, epigenetic regulation, and disease pathophysiology. These insights also highlight the interplay between metabolic and epigenetic reprogramming during septic progression. As a result, lactylation has emerged as a promising biomarker and potential therapeutic target in sepsis. This review aims to summarize the latest findings on lactate metabolism, lactylation modifications, and their immunometabolic implications in sepsis.