Contribution of the Environment, Epigenetic Mechanisms and Non-Coding RNAs in Psoriasis

Abstract

Despite the increasing research and clinical interest in the predisposition of psoriasis, a chronic inflammatory skin disease, the multitude of genetic and environmental factors involved in its pathogenesis remain unclear. This complexity is further exacerbated by the several cell types that are implicated in Psoriasis’s progression, including keratinocytes, melanocytes and various immune cell types. The observed interactions between the genetic substrate and the environment lead to epigenetic alterations that directly or indirectly affect gene expression. Changes in DNA methylation and histone modifications that alter DNA-binding site accessibility, as well as non-coding RNAs implicated in the post-transcriptional regulation, are mechanisms of gene transcriptional activity modification and therefore affect the pathways involved in the pathogenesis of Psoriasis. In this review, we summarize the research conducted on the environmental factors contributing to the disease onset, epigenetic modifications and non-coding RNAs exhibiting deregulation in Psoriasis, and we further categorize them based on the under-study cell types. We also assess the recent literature considering therapeutic applications targeting molecules that compromise the epigenome, as a way to suppress the inflammatory cutaneous cascade.

Intrinsic Effects of Exposome in Atopic Dermatitis: Genomics, Epigenomics and Regulatory Layers

“…Epigenetic modifications refer to alterations in the DNA sequence that orchestrate gene expression via modulating the accessibility of the transcriptional machinery through the addition of a methyl group to the C5 position of cytosine, resulting in the formation of 5-methylcytosine (5mC). On the contrary, demethylation of 5mC occurs through two processes, including ten-eleven translocation (TET) enzymes that form an intermediate product called 5-hydroxymethylcytosine (5hmC), and deamination of 5mC followed by the base excision repair (BER) pathway [ 44 ].…”