Lactylation: a novel epigenetic bridge connecting metabolic reprogramming and immune dysregulation in...

Sepsis-associated acute respiratory distress syndrome (ARDS) is driven by metabolic reprogramming and immune dysregulation, but the molecular link between them remains unclear. Lactylation, a lactate-derived post-translational modification, couples metabolic state to transcriptional and functional outcomes in immune and parenchymal cells as an epigenetic reader of glycolytic flux. Recent evidence demonstrates that lactylation regulates macrophage polarization, neutrophil extracellular trap formation, myeloid derived suppressor cell function, and T cell differentiation, while also controlling ferroptosis, autophagy, and endothelial injury in the septic lung. Clinical studies have identified histone H3K18 lactylation as a potential biomarker for sepsis severity and prognosis. This review establishes lactylation as a novel epigenetic bridge connecting metabolic reprogramming and immune dysregulation in sepsis associated ARDS and highlights therapeutic opportunities targeting this modification.