Histone lactylation: a metabolic-epigenetic bridge linking glycolysis to salivary gland fibrosis in Sjögren's disease.

Sjögren's disease (SjD) is a chronic, systemic autoimmune disorder characterized by lymphocytic infiltration and progressive loss of exocrine gland function. Despite advances in understanding its immunopathogenesis, the molecular mechanisms governing the transition from inflammation to irreversible salivary gland fibrosis remain obscure. Emerging evidence suggests that the crosstalk between metabolic reprogramming and epigenetic modifications profoundly shapes the local inflammatory microenvironment and accelerates disease progression. Histone lactylation, a recently discovered lactate-derived epigenetic mark, directly couples enhanced glycolytic activity and lactate accumulation with transcriptional regulation, thereby serving as a pivotal metabolic-epigenetic bridge. This review systematically examines the potential role of histone lactylation in SjD salivary gland pathology. We delineate the enzymatic machinery of lactylation, the metabolic origins of lactate within the inflamed microenvironment, and the functional implications for immune cell polarization, epithelial-mesenchymal transition, and myofibroblast activation. While direct evidence in SjD is currently lacking, we synthesize findings by integrating immunometabolism, epigenetic rewiring, and tissue fibrogenesis, we aim to establish histone lactylation as a transformative framework for understanding SjD pathogenesis and highlight its translational potential for novel biomarkers and therapeutic interventions.