Epigenetic regulatory mechanisms of autoimmune skin diseases: novel biomarkers and therapeutic prospects

Autoimmune skin diseases (AISDs) are disorders characterized by disrupted immune tolerance and aberrant responses against skin antigens, including atopic dermatitis (AD), psoriasis, systemic lupus erythematosus (SLE), bullous pemphigoid (BP), and other common conditions. Dysregulated expression of immune-related genes-particularly those governing B and T cell functions-holds promise as diagnostic and prognostic biomarkers, though their regulatory mechanisms remain incompletely defined. This review systematically synthesizes recent evidence elucidating the central role of three core epigenetic mechanisms-DNA methylation, histone modifications (including emerging metabolically linked alterations), and noncoding RNAs (ncRNAs)-in driving AISD pathogenesis. We highlight the dynamic interplay between epigenetic dysregulation, immune dysfunction, and skin barrier impairment. Deciphering these epigenetic networks and identifying key regulators (e.g., DNMTs, histone-modifying enzymes, ncRNAs) may enable high-precision diagnostics and novel therapies to restore immune homeostasis. Such advances will deepen mechanistic insights and transform clinical management paradigms.