Stromal cells and epigenetics: emerging key players of chronic inflammatory skin diseases

Abstract

Epigenetic alterations play a crucial role in developmental processes, tissue regeneration, and cellular differentiation. Epigenetic changes are dynamically reversible. Various drugs that target DNA methyltransferases or histone deacetylases have demonstrated their ability to restore normal epigenetic patterns in a number of diseases. While the involvement of epigenetic modifications has been identified in chronic inflammatory diseases, their specific impact on skin inflammation in stromal cells remains unclear. This mini-review explores the role of stromal cells in chronic inflammatory skin diseases, focusing on epigenetic modifications of stromal cells such as fibroblasts, lymphatic, and blood vascular endothelial cells in both healthy and diseased skin. We also provide an overview of recent findings that highlight the contribution of stromal cells, including fibroblasts, to inflammatory and remodeling processes through epigenetic changes in the context of chronic inflammatory conditions. Investigating epigenetic reprogramming of stromal cells might lead to novel strategies for treating chronic inflammatory skin diseases. [BMB Reports 2024; 57(11): 465-471].

Fig. 1

Heterogeneity of stromal cells in chronic inflammatory disease. Subpopulations of stromal cells, including fibroblasts, blood vascular endothelial cells (BECs), and lymphatic endothelial cells (LECs), identified from single-cell transcriptomics, display specific molecular repatterning, potentially leading to activated states. Activated stromal cells can trigger cytokine/chemokine responses, enhance T-cell persistence, and alter extracellular matrix (ECM) components relevant to the pathogenesis of chronic inflammatory skin diseases.

Fig. 2

Flexibility of epigenetic signatures by epigenetic reprogramming. DNA can undergo methylation at cytosine residues in a CpG context (DNA methylation). The DNA wraps around histone proteins to form structures called nucleosomes. Modifications to these histone proteins represent another layer of epigenetic regulations (histone acetylation/methylation). These modifications dictate whether the chromatin structure is open and accessible or closed and inaccessible. Acetylation of histone tails by histone acetyltransferase (HAT) activates genes, whereas histone deacetylation by deacetylases (HDACs) leads to gene silencing. DNA methyltransferase (DNMTs) adds methyl groups to the 5-position of cytosine residues in DNA, crucial for the process of DNA methylation, playing a significant role in maintaining genome stability.