Train your histones

IF 27.6 1区医学 Q1 IMMUNOLOGY

Nature Immunology Pub Date : 2025-06-30 DOI:10.1038/s41590-025-02214-7

Laurie A. Dempsey

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引用次数: 0

Abstract

Previous cellular experiences can be remembered by epigenetic modifications of chromatin, which can then promote or impair subsequent cellular responses. This epigenetic memory process underlies the concept of ‘trained immunity’ that occurs in innate immune cells. In Cell, Ziogas et al. show that monocytes from humans vaccinated with Bacille Calmette-Guérin (BCG) undergo long-term epigenetic reprogramming that involves histone H3 lactylation on lysine 18 (H3K18la). BCG-induced training increases intracellular lactate production, in part by increasing expression of PKM, LDHA and LDHB. After BCG stimulation, the chromatin modifier p300–CBP promotes H3K18la post-translational modifications, which mainly occur at distal enhancers — in particular, at loci enriched for bZIP transcription factor motifs and CTCF-binding sites. Notably, this response seems to rely on intracellular lactate sources. This H3K18la memory response is associated with increased cytokine and chemokine gene expression that can persist for months after initial stimulation. These findings provide mechanistic underpinnings for the BCG-mediated trained immune effects.

Original reference: Cell 188, 2992–3012 (2025)

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训练组蛋白

以前的细胞经历可以通过染色质的表观遗传修饰来记住，这可以促进或损害随后的细胞反应。这种表观遗传记忆过程是先天免疫细胞中“训练免疫”概念的基础。在Cell中，Ziogas等人表明，接种卡介苗（BCG）的人单核细胞经历了长期的表观遗传重编程，涉及赖氨酸18 （H3K18la）上的组蛋白H3乳酸化。bcg诱导的训练增加细胞内乳酸生成，部分是通过增加PKM、LDHA和LDHB的表达。在BCG刺激后，染色质修饰子p300-CBP促进H3K18la翻译后修饰，这些修饰主要发生在远端增强子上，特别是在bZIP转录因子基元和ctcf结合位点富集的位点上。值得注意的是，这种反应似乎依赖于细胞内乳酸源。这种H3K18la记忆反应与细胞因子和趋化因子基因表达的增加有关，这种增加可以在初始刺激后持续数月。这些发现为bcg介导的训练免疫效应提供了机制基础。原始参考文献：188,2992 - 3012单元（2025）

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature Immunology 医学-免疫学

CiteScore

40.00

自引率

2.30%

发文量

248

审稿时长

4-8 weeks

期刊介绍： Nature Immunology is a monthly journal that publishes the highest quality research in all areas of immunology. The editorial decisions are made by a team of full-time professional editors. The journal prioritizes work that provides translational and/or fundamental insight into the workings of the immune system. It covers a wide range of topics including innate immunity and inflammation, development, immune receptors, signaling and apoptosis, antigen presentation, gene regulation and recombination, cellular and systemic immunity, vaccines, immune tolerance, autoimmunity, tumor immunology, and microbial immunopathology. In addition to publishing significant original research, Nature Immunology also includes comments, News and Views, research highlights, matters arising from readers, and reviews of the literature. The journal serves as a major conduit of top-quality information for the immunology community.