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Curr Opin Cell Biol. 2020 Jan 25;63:68-75. doi: 10.1016/j.ceb.2019.12.006. [Epub ahead of print]

Advances in understanding molecular regulation of innate immune memory.

Author information

1
Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Nijmegen Medical Centre, Geert Grooteplein 8, 6500HB, Nijmegen, the Netherlands; Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, 6525, GA, Nijmegen, the Netherlands. Electronic address: jorge.dominguezandres@radboudumc.nl.
2
Division of Chemical, Systems & Synthetic Biology, Department of Integrative Biomedical Sciences, Faculty of Health Sciences, Institute of Infectious Disease & Molecular Medicine, University of Cape Town, Cape Town, South Africa; Gene Expression and Biophysics Group, ERA, CSIR Biosciences, Pretoria, South Africa. Electronic address: parrucchiere@mhlangalab.org.
3
Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Nijmegen Medical Centre, Geert Grooteplein 8, 6500HB, Nijmegen, the Netherlands; Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, 6525, GA, Nijmegen, the Netherlands; Department of Medical Genetics, Iuliu Hatieganu University of Medicine and Pharmacy, 400349, Cluj-Napoca, Romania.
4
Division of Chemical, Systems & Synthetic Biology, Department of Integrative Biomedical Sciences, Faculty of Health Sciences, Institute of Infectious Disease & Molecular Medicine, University of Cape Town, Cape Town, South Africa; Gene Expression and Biophysics Unit, Instituto de Medicina Molecular, Faculdade de Medicina Universidade de Lisboa, Lisbon, Portugal.
5
Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Nijmegen Medical Centre, Geert Grooteplein 8, 6500HB, Nijmegen, the Netherlands; Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, 6525, GA, Nijmegen, the Netherlands; Department for Immunology & Metabolism, Life and Medical Sciences Institute (LIMES), University of Bonn, 53115 Bonn, Germany.

Abstract

The epigenetic and functional reprogramming of immune genes during induction of trained immunity is accompanied by the metabolic rewiring of cellular state. This memory is induced in the hematopoietic niche and propagated to daughter cells, generating epigenetically and metabolically reprogrammed innate immune cells that are greatly enhanced in their capacity to resolve inflammation. In particular, these cells show accumulation of H3K4me3 and H3K27Ac epigenetic marks on multiple immune gene promoters and associated enhancers. However, the mechanism governing how these epigenetic marks accumulate at discrete immune gene loci has been poorly understood, until now. Here, we discuss some recent advances in the regulation of trained immunity, with a particular focus on the mechanistic role of a novel class of long non-coding RNAs in the establishment of epigenetic marks on trained immune gene promoters.

KEYWORDS:

Epigenetics; Innate memory; Macrophages; Metabolism; Monocytes; Stem cells; TADs; Trained immunity; lncRNA

PMID:
31991317
DOI:
10.1016/j.ceb.2019.12.006

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