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Front Cell Dev Biol. 2019 Jan 24;7:2. doi: 10.3389/fcell.2019.00002. eCollection 2019.

Lnc-ing Trained Immunity to Chromatin Architecture.

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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, CSIR Biosciences, Pretoria, 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.


BCG—Bacille Calmette-Guérin vaccine; LncRNA—long non-coding RNA; chromatin; epigenetic memory; innate immunity; macrophages; trained immunity; transcriptional (regulation)

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