Mechanistic aspects of epigenetic dysregulation in SLE

Abstract

Epigenetic events have been linked with disease expression in individuals genetically predisposed to the development of systemic lupus erythematosus (SLE), a severe systemic autoimmune/inflammatory disease. Altered DNA methylation and hydroxymethylation as well as histone modifications mediate changes in chromatin accessibility and gene expression in immune cells from SLE patients. Defective epigenetic control contributes to uncontrolled expression of inflammatory mediators, including cytokines and co-receptors, resulting in systemic inflammation and tissue damage. While the pathophysiological involvement of epigenetic changes in SLE has been accepted for some time, we only recently started to investigate and understand molecular events contributing to epigenetic dysregulation. Here, epigenetic alterations will be discussed with a focus on underling molecular events that may be target of preventative measures or future treatment strategies.

Keywords: CREMα; Chromatin; DNA hydroxymethylation; DNA methylation; Environment; Epigenetic; Histone; Inflammation; Remodeling; Systemic lupus erythematosus.