Table 1_Glycolytic reprogramming and cell-specific lactylation in asthma: an evidence-graded framework for testable metabolic-epigenetic profiles.docx

This review addresses that problem by organizing glycolytic reprogramming and lysine lactylation through a three-tier hierarchy: human asthma observations, mechanistic perturbation in asthma-relevant models, and cross-disease or conceptual precedents.

Mitochondrial and redox disturbances alter glycolytic and oxidative capacity across immune and structural cells, whereas lactate can function separately as an exported acidifying metabolite and as an intracellular substrate for site-specific lactylation. Four asthma-associated circuits have the strongest direct mechanistic support: epithelial histone H3 lysine 18 lactylation (H3K18la)–colony-stimulating factor 1 receptor (CSF1R) signaling; cluster of differentiation 4-positive (CD4⁺) T-cell H3K18la–dipeptidyl peptidase 4 (DPP4) regulation; mitochondrial phosphoenolpyruvate carboxykinase 2 (PCK2)-dependent polyglutamine-binding protein 1 (PQBP1) K223 lactylation coupled to protein arginine methyltransferase 5 (PRMT5) inhibition; and macrophage sirtuin 6 (SIRT6)–lactate dehydrogenase A (LDHA)–histone H4 lysine 12 lactylation (H4K12la) signaling.