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Front. Immunol. | doi: 10.3389/fimmu.2019.02718

Metabolic control of epigenetics and its role in CD8+ T cell differentiation and function

  • 1Department of Gastroenterology, Nephrology and Metabolic Diseases, Charité Medical University of Berlin, Germany
  • 2Department of Biology, Chemistry and Pharmacy, Free University of Berlin, Germany
  • 3Berlin Institute of Health Research (BIH), Germany

Epigenetic programs that control posttranslational modifications of histone proteins and DNA itself tightly regulate transcriptional networks determining the identity and function of CD8+ T cells. Chromatin-modifying enzymes such as histone acetyltransferases and deacetylases, represent key molecular determinants of the epigenetic imprinting of CD8+ T cells. The functions of these enzymes highly depend on the availability of key products of cellular metabolism pathways such as acetyl-CoA, NAD (Nicotinamide adenine dinucleotide), SEM (S-adenosylmethionine), suggesting that there is a close crosstalk between the metabolic and the epigenetic regulation of CD8+ T cells. In this review, we will discuss the metabolic regulation of CD8+ T cell epigenetics during activation and differentiation. We will furthermore summarize how metabolic signals from the tumor microenvironment (TME) shape the epigenetic landscape of CD8+ T cells to better understand the mechanism underlying CD8+ T cell exhaustion in anti-tumor and anti-viral immunity, which might help to overcome limitations of current CD8+ T cell-based therapies.

Keywords: epigenetics, Metabolism, CD8 T cell, exhaustion, anti-tumor immunity, anti-viral immunity

Received: 20 Jun 2019; Accepted: 05 Nov 2019.

Copyright: © 2019 Yerinde, Siegmund, Glauben and Weidinger. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Rainer Glauben, Department of Gastroenterology, Nephrology and Metabolic Diseases, Charité Medical University of Berlin, Berlin, Germany, rainer.glauben@charite.de