Epigenetic‐modifying therapies: An emerging avenue for the treatment of inflammatory skin diseases

Abstract

Epigenetic modifications include DNA methylation, histone modification and the action of microRNAs. These mechanisms coordinate in complex networks to control gene expression, thereby regulating key physiological processes in the skin and immune system. Recently, researchers have turned to the epigenome to understand the pathogenesis of inflammatory skin diseases. In psoriasis and atopic dermatitis, epigenetic modifications contribute to key pathogenic events such as immune activation, T-cell polarization and keratinocyte dysfunction. These discoveries have introduced new possibilities for the treatment of skin diseases; unlike genetics, epigenetic alterations are readily modifiable and potentially reversible. In this viewpoint essay, we summarize the current state of epigenetic research in inflammatory skin diseases and propose that targeting the histone machinery is a promising avenue for the development of new therapies for psoriasis and atopic dermatitis. Expanding on the progress that has already been made in the field of cancer epigenetics, we discuss existing epigenetic-modifying tools that can be applied to the treatment of inflammatory skin diseases and consider future directions for investigation in order to allow for the widespread clinical application of such therapies.

MicroRNA profiling of psoriatic skin identifies 11 miRNAs associated with disease severity

“…Further, several DEMs have been shown to have central roles in psoriasis pathophysiology, including miR‐31 which increases production of tumor necrosis factor (TNF) 18 and miR‐21 which leads to chronic inflammation in patients with psoriasis 18 . In addition, specific miRNAs show promise as sensitive biomarkers for psoriasis disease activity, prognosis and treatment response, 19 as well as targets for epigenetic‐modifying therapies 20 . Examples include miR‐146a whose levels correlate with increasing psoriasis severity 21 .…”

Skin epigenetics

“…Jean McGee and colleagues review epigenetic-modifying therapies in inflammatory skin diseases. 55 The authors point to precedent in the cancer field where the roles of epigenetic mechanisms have been clearly revealed, with epigenetic therapies advancing to clinical care such as for histone deacetylase inhibitors in cutaneous T-cell lymphoma.…”

“…Preclinical studies on histone deacetylase (HDAC) and bromodomain and extraterminal (BET) inhibitors show promise for the treatment of psoriasis and atopic dermatitis. The data summarized in these three reviews [53][54][55] clearly demonstrate that metabolism [56][57][58][59] and its connection to epigenetics is an exciting emerging research area in inflammatory skin diseases.…”

HDAC6 and CXCL13 Mediate Atopic Dermatitis by Regulating Cellular Interactions and Expression Levels of miR-9 and SIRT1

“…In addition to gene mutations, epigenetic modifications contribute to the pathogenesis of AD ( Yi and Mcgee, 2021 ). Epigenetic modifications include DNA methylations, histone modifications, and microRNAs.…”