Epigenetic Dysregulation and its Role in Immune-Mediated Diseases

Abstract

Immune-mediated diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS) and Inflammatory Bowel Disease (IBD: Crohn's Disease & Ulcerative Colitis) represent a significant global health burden characterized by a loss of immune tolerance and chronic inflammation. While genetic predisposition plays a crucial role, it does not fully account for disease pathogenesis, onset, or flare-ups. The emerging field of epigenetics provides a critical mechanistic link between genetic susceptibility and environmental triggers. This review synthesizes current evidence on how dysregulation of key epigenetic mechanisms, DNA methylation, histone modifications, and non-coding RNA expression, contributes to the breakdown of immune homeostasis. We detail the aberrant epigenetic landscapes in specific immune cell subsets (e.g., T cells, B cells, macrophages) across major autoimmune disorders. Furthermore, we explore the potential of epigenetic modifications as novel biomarkers for diagnosis, prognosis, and disease activity monitoring. Finally, we discuss the promising therapeutic avenue of "epigenetic therapy," repurposing existing drugs and developing new compounds to reverse pathogenic epigenetic marks and restore immune tolerance.