Epigenetic reprogramming of immune cells in injury, repair, and resolution
Katarzyna Placek, … , Joachim L. Schultze, Anna C. Aschenbrenner
Katarzyna Placek, … , Joachim L. Schultze, Anna C. Aschenbrenner
Published August 1, 2019; First published July 22, 2019
Citation Information: J Clin Invest. 2019;129(8):2994-3005. https://doi.org/10.1172/JCI124619.
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Review Series

Epigenetic reprogramming of immune cells in injury, repair, and resolution

Abstract

Immune cells are pivotal in the reaction to injury, whereupon, under ideal conditions, repair and resolution phases restore homeostasis following initial acute inflammation. Immune cell activation and reprogramming require transcriptional changes that can only be initiated if epigenetic alterations occur. Recently, accelerated deciphering of epigenetic mechanisms has extended knowledge of epigenetic regulation, including long-distance chromatin remodeling, DNA methylation, posttranslational histone modifications, and involvement of small and long noncoding RNAs. Epigenetic changes have been linked to aspects of immune cell development, activation, and differentiation. Furthermore, genome-wide epigenetic landscapes have been established for some immune cells, including tissue-resident macrophages, and blood-derived cells including T cells. The epigenetic mechanisms underlying developmental steps from hematopoietic stem cells to fully differentiated immune cells led to development of epigenetic technologies and insights into general rules of epigenetic regulation. Compared with more advanced research areas, epigenetic reprogramming of immune cells in injury remains in its infancy. While the early epigenetic mechanisms supporting activation of the immune response to injury have been studied, less is known about resolution and repair phases and cell type–specific changes. We review prominent recent findings concerning injury-mediated epigenetic reprogramming, particularly in stroke and myocardial infarction. Lastly, we illustrate how single-cell technologies will be crucial to understanding epigenetic reprogramming in the complex sequential processes following injury.

Authors

Katarzyna Placek, Joachim L. Schultze, Anna C. Aschenbrenner

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Figure 3

Integrated view of the epigenetic processes occurring over time during injury, repair, and resolution.

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Integrated view of the epigenetic processes occurring over time during i...
Epigenetic regulatory mechanisms can be studied on the level of population, individual, and tissues and organs, as well as the single-cell level. Since any injury is followed by a sequence of processes ranging from immune system activation to peak reactivity to repair and resolution, time-resolved analyses of epigenetic processes are required. At the different levels (population, individuals, tissues and organs, and single cells), different multi-omics approaches can be applied to determine epigenetic regulation. Resolution, complexity that can be determined, scalability of epigenetic assays, and costs of analyses differ substantially between the different settings. Future studies particularly targeting the repair and resolution phases will require sophisticated planning of overall goals and experiments to be performed. eQTL, expression quantitative trait loci; epiQTL, epigenetic quantitative trait loci.