Department of Dermatology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
Exp Dermatol. 2021 Aug;30(8):1167-1176. doi: 10.1111/exd.14334. Epub 2021 Apr 5.
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.
表观遗传修饰包括 DNA 甲基化、组蛋白修饰和 microRNA 的作用。这些机制在复杂的网络中协同作用，控制基因表达，从而调节皮肤和免疫系统中的关键生理过程。最近，研究人员开始关注表观基因组，以了解炎症性皮肤病的发病机制。在银屑病和特应性皮炎中，表观遗传修饰有助于免疫激活、T 细胞极化和角质形成细胞功能障碍等关键发病事件。这些发现为皮肤病的治疗带来了新的可能性；与遗传学不同，表观遗传改变易于修饰且具有潜在的可逆性。在这篇观点文章中，我们总结了炎症性皮肤病中表观遗传学研究的现状，并提出靶向组蛋白机制是开发银屑病和特应性皮炎新疗法的有前途的途径。在癌症表观遗传学领域已经取得的进展的基础上，我们讨论了可应用于治疗炎症性皮肤病的现有表观遗传修饰工具，并考虑了未来的研究方向，以使这些疗法能够广泛应用于临床。
