Fanucchi Stephanie, Mhlanga Musa M
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.
Front Cell Dev Biol. 2019 Jan 24;7:2. doi: 10.3389/fcell.2019.00002. eCollection 2019.
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.
暴露于某些感染或刺激的人类先天免疫细胞在再次受到不同的第二种刺激感染时会产生增强的免疫反应，这一过程称为训练免疫。最近的研究表明，造血干细胞（HSCs）对于训练免疫反应至关重要，因为它们能够“记住”转录反应并将这种状态传递给它们的后代，以指导它们如何应对未来的感染。来自受过训练的造血干细胞的巨噬细胞在表观遗传上被重新编程，因此能够强力表达免疫基因，增强其解决感染的能力。在训练免疫反应期间，多个免疫基因启动子上H3K4me3表观遗传标记的积累是强力转录反应的基础。然而，这些表观遗传标记如何在离散的免疫基因位点积累的机制仍知之甚少。在这篇综述中，我们讨论了核结构和长链非编码RNA在训练免疫中对H3K4me3启动子引发的此前未被探索的作用。改变这些长链非编码RNA的活性为在炎症性疾病状态下实现免疫调节提供了一种有前景的治疗方法。
