1 Department of Internal Medicine, Radboud University Medical Center , Nijmegen, The Netherlands .
2 Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn , Bonn, Germany .
Antioxid Redox Signal. 2018 Oct 10;29(11):1023-1040. doi: 10.1089/ars.2017.7310. Epub 2017 Nov 21.
A growing body of clinical and experimental evidence has challenged the traditional understanding that only the adaptive immune system can mount immunological memory. Recent findings describe the adaptive characteristics of the innate immune system, underscored by its ability to remember antecedent foreign encounters and respond in a nonspecific sensitized manner to reinfection. This has been termed trained innate immunity. Although beneficial in the context of recurrent infections, this might actually contribute to chronic immune-mediated diseases, such as atherosclerosis. Recent Advances: In line with its proposed role in sustaining cellular memories, epigenetic reprogramming has emerged as a critical determinant of trained immunity. Recent technological and computational advances that improve unbiased acquisition of epigenomic profiles have significantly enhanced our appreciation for the complexities of chromatin architecture in the contexts of diverse immunological challenges.
Key to resolving the distinct chromatin signatures of innate immune memory is a comprehensive understanding of the precise physiological targets of regulatory proteins that recognize, deposit, and remove chemical modifications from chromatin as well as other gene-regulating factors. Drawing from a rapidly expanding compendium of experimental and clinical studies, this review details a current perspective of the epigenetic pathways that support the adapted phenotypes of monocytes and macrophages.
We explore future strategies that are aimed at exploiting the mechanism of trained immunity to improve the prevention and treatment of infections and immune-mediated chronic disorders.
越来越多的临床和实验证据挑战了传统观念，即只有适应性免疫系统才能产生免疫记忆。最近的发现描述了先天免疫系统的适应性特征，其特点是能够记住先前的外来接触，并以非特异性致敏的方式对再感染作出反应。这被称为训练有素的先天免疫。虽然在反复感染的情况下是有益的，但这实际上可能导致慢性免疫介导的疾病，如动脉粥样硬化。最新进展：与其在维持细胞记忆中的作用一致，表观遗传重编程已成为训练有素的免疫的关键决定因素。最近在技术和计算方面的进展，提高了对表观基因组图谱的无偏获取，这大大提高了我们对不同免疫挑战背景下染色质结构复杂性的认识。
要确定先天免疫记忆的独特染色质特征，关键是要全面了解识别、沉积和去除染色质化学修饰的调节蛋白以及其他基因调节因子的确切生理靶点。本文从迅速扩展的实验和临床研究纲要中详细阐述了支持单核细胞和巨噬细胞适应性表型的表观遗传途径的当前观点。
我们探讨了未来的策略，旨在利用训练有素的免疫机制来改善感染和免疫介导的慢性疾病的预防和治疗。
