Chromatin Architecture as an Essential Determinant of Dendritic Cell Function

Abstract

Epigenetics has widespread implications in a variety of cellular processes ranging from cell identity and specification, to cellular adaptation to environmental stimuli. While typically associated with heritable changes in gene expression, epigenetic mechanisms are now appreciated to regulate dynamic changes in gene expression—even in post-mitotic cells. Cells of the innate immune system, including dendritic cells (DC), rapidly integrate signals from their microenvironment and respond accordingly, undergoing massive changes in transcriptional programming. This dynamic transcriptional reprogramming relies on epigenetic changes mediated by numerous enzymes and their substrates. This review highlights our current understanding of epigenetic regulation of DC function. Epigenetic mechanisms contribute to the maintenance of the steady state and are important for precise responses to proinflammatory stimuli. Interdependence between epigenetic modifications and the delicate balance of metabolites present another layer of complexity. In addition, dynamic regulation of the expression of proteins that modify chromatin architecture in DCs significantly impacts DC function. Environmental factors, including inflammation, aging, chemicals, nutrients, and lipid mediators, are increasingly appreciated to affect the epigenome in DCs, and, in doing so, regulate host immunity. Our understanding of how epigenetic mechanisms regulate DC function is in its infancy, and it must be expanded in order to discern the mechanisms underlying the balance between health and disease states.

Epigenetic modulation of antitumor immunity for improved cancer immunotherapy

“…DCs rapidly integrate signals from their tissue microenvironments and respond accordingly to these signals, undergoing dramatic changes in transcriptional programming as a consequence of environmental stressors. This dynamic change relies on epigenetic changes in the chromatin structure of DCs as mediated by numerous enzymes and their substrates [ 124 ]. However, gene activation precedes DNA demethylation in response to infection in human DCs.…”

Transcriptional Networks Driving Dendritic Cell Differentiation and Function

“…Several classes of histone modifying enzymes have also been implicated in DC differentiation and activation (reviewed by Boukhaled et al, 2019). These modifications collectively result in huge changes in the chromatin accessibility across the DC lineages (Bornstein et al, 2014;Lin et al, 2015;Yoshida et al, 2019).…”

Effects and mechanisms of Portulaca oleracea L. polysaccharides on the activation of dendritic cells derived from mice immunized with FMD vaccine

“…Recent studies have demonstrated that the differentiation, maturation and function of DCs are not only in uenced by extracellular factors and intracellular genetic factors, but also regulated by epigenetics [21,22]. Under the action of speci c signals, including drug components, DCs could undergo epigenetic regulation to determine its maturation process and mechanism [23]. At present, there are no landmark studies on the regulation of DCs by epigenetic modi cation factors from the perspective of DCs speci c function.…”