The role of microRNAs in primary Sjögren’s disease: deciphering regulatory networks and assessing current therapeutic perspectives

Primary Sjögren's disease (SjD) is a chronic systemic autoimmune disorder whose pathogenesis remains incompletely understood. Current clinical interventions demonstrate limited efficacy, yielding suboptimal therapeutic outcomes. microRNAs (miRNAs)-critical regulators of transcriptional networks-participate in SjD pathogenesis through multifaceted mechanisms. Dysregulated miRNA expression during SjD progression directly influences disease prognosis, establishing miRNAs as promising therapeutic targets. Evidence implicates macrophage polarization, apoptosis dysregulation, Th17/Treg imbalance, T/B lymphocyte dysfunction, glandular impairment, and aberrant type I interferon responses in SjD development. Notably, miR-216a-3p, miR-31-5p, and miR-155-5p modulate key signaling pathways (NF-κB, JAK/STAT, PI3K/AKT) to optimize macrophage polarization, suppress apoptosis, restore Th17/Treg equilibrium, regulate T/B lymphocyte activity, enhance glandular function, normalize type I interferon responses,thereby exerting potent anti-SjD effects. This review synthesizes recent literature to elucidate SjD pathogenesis and miRNA-mediated therapeutic mechanisms, providing a theoretical foundation for novel SjD management strategies.