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Chromatin Traits in Human Diseases

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Front. Cell Dev. Biol. | doi: 10.3389/fcell.2019.00002

Lnc-ing trained immunity to chromatin architecture

  • 1University of Cape Town, South Africa
  • 2Council for Scientific and Industrial Research (CSIR), South Africa

Human innate immune cells exposed to certain infections or stimuli develop enhanced immune responses upon re-infection with a different second stimulus, a process termed trained immunity. Recent studies have revealed that hematopoietic stem cells (HSCs) are integral to trained immune responses as they are able to ‘remember’ transcriptional responses and transmit this state to their progeny to educate them how to respond to future infections. The macrophages that arise from trained HSCs are epigenetically reprogrammed and as a result robustly express immune genes, enhancing their capability to resolve infection. Accumulation of H3K4me3 epigenetic marks on multiple immune gene promoters underlie robust transcriptional responses during trained immune responses. However, the mechanism underpinning how these epigenetic marks accumulate at discrete immune gene loci has been poorly understood. In this review we discuss the previously unexplored contributions of nuclear architecture and long non coding RNAs on H3K4me3 promoter priming in trained immunity. Altering the activity of these lncRNAs presents a promising therapeutic approach to achieve immunomodulation in inflammatory disease states.

Keywords: LncRNA - long noncoding RNA, Chromatin, trained immunity, Transcriptional (regulation), Innate immnuity, Epigenetic memory, Macrophages, BCG - Bacille Calmette-Guérin vaccine

Received: 13 Sep 2018; Accepted: 10 Jan 2019.

Edited by:

Marina Lusic, Universität Heidelberg, Germany

Reviewed by:

Girdhari Lal, National Centre for Cell Science (NCCS), India
Jingying Zhou, The Chinese University of Hong Kong, China
Michael Robson, Max Planck Institute for Molecular Genetics, Germany  

Copyright: © 2019 Fanucchi and Mhlanga. 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. Stephanie Fanucchi, University of Cape Town, Cape Town, 7701, South Africa, steph@mhlangalab.org
Prof. Musa M. Mhlanga, University of Cape Town, Cape Town, 7701, South Africa, musa@mhlangalab.org