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接种BCG疫苗会影响人类骨髓中原生细胞的表观遗传情景

Sarah J Sun^1,2, Raúl Aguirre-Gamboa³, L Charlotte J de Bree⁴

¹Committee on Immunology, University of Chicago, Chicago, IL, USA.

bioRxiv : the preprint server for biology

|December 11, 2023

概括

细菌-卡尔梅特-盖林 (BCG) 疫苗改变了人类干细胞的基因表达和表观遗传学,增强了髓质偏差并影响了免疫反应. 这为BCG提供了新的见解.

科学领域:

免疫学免疫学免疫学
血液形成血液形成血液形成
表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.

背景情况:

细菌-卡尔梅特-盖林 (BCG) 疫苗可以预防结核病,但也可以保护其他感染.
在人类中,BCG的广谱保护背后的机制,特别是它对免疫系统的基础细胞的影响,仍然不清楚.

研究的目的:

研究BCG疫苗接种对人类造血干细胞和原生细胞 (HSPCs) 的单细胞分离效应.
了解BCG对基因表达,染色体景观和先天免疫记忆的影响.

主要方法:

在BCG疫苗接种或安慰剂之前和90天后对人类骨髓样本的分析.
单细胞RNA测序和ATAC测序用于调查基因表达和染色质可访问性.
在HSPC变化和外围血液单核细胞 (PBMC) 细胞因子分泌之间的相关性分析.

主要成果:

接种BCG疫苗会显著改变HSPC的基因表达和表观遗传特征,导致持续的髓状偏差.
染色质可访问性的变化在差异化的原始细胞中突出,由转录因子 (KLF/SP,EGR) 驱动,这些转录因子也在干细胞中活跃.
在二次免疫挑战时,HSPC变化与增强的IL-1β分泌能力有很强的相关性.

结论:

接种BCG疫苗会诱导HSPCs的持久变化,挑战直接干系到衍生物的表观遗传记忆传输模型.
这些HSPC修改与改善的先天免疫反应有关,这解释了BCG保护作用的一部分.
研究结果揭示了BCG对免疫系统早期细胞组成部分的显著影响.

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