Immune System Disorders and Epigenetics

Mehta, S.; Jeffrey, K.L.

Our understanding of epigenetics in complex diseases is rapidly advancing and increasingly influencing the practice of medicine. Much is known about disruption of chromatin-modifying enzymes in malignant disease, but knowledge of irregular epigenetics in immune-driven disorders is just emerging. Epigenetic factors, such as DNA or histone modifications, are indispensable for precise gene expression in diverse immune cell types. Thus a disruption of epigenetic landscapes likely has a large impact on immune homeostasis. Moreover, the low concordance rates for most autoimmune diseases suggest that epigenetics contribute to immune tolerance disturbance. Here we review the important role of epigenetics for initiation, maintenance, tolerance, and training of immune responses. We discuss evolving evidence that DNA/histone modifications and chromatin-modifying enzymes are altered in immune-based diseases. Furthermore, we explore the potential of small molecules targeting epigenetic machinery, some of which are already used in oncology, as a way to reset the immune response in disease.