The epigenomic landscape of bronchial epithelial cells reveals the establishment of trained immunity.

IF 4.5 3区 医学 Q1 GENETICS & HEREDITY
Jeanne Bigot, Rachel Legendre, Juliette Hamroune, Sébastien Jacques, Mathieu Le Gars, Nicolas Millet, Loïc Guillot, Harriet Corvol, Christophe Hennequin, Juliette Guitard, Jean-Yves Coppée, Viviane Balloy, Claudia Chica
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引用次数: 0

Abstract

Innate immune memory, also called trained immunity, refers to the ability of innate immune cells to gain memory characteristics after transient stimulation, resulting in a nonspecific modified inflammatory response upon secondary remote challenge. Bronchial epithelial cells (BECs) participate in innate immune defence and are the first cells of the lower respiratory tract to encounter inhaled pathogens. We recently showed that BECs are capable of innate immune memory after preexposure to Pseudomonas aeruginosa flagellin through epigenetic mechanisms. In the present study, we investigated such mechanisms through the modification of chromatin architecture induced by flagellin preexposure that results in subsequent changes of gene expression. By conducting an unsupervised approach to jointly analyse chromatin accessibility and gene expression, we mapped the remodelling of the epigenomic and transcriptomic profiles during the establishment of BECs memory. We identified a Memory regulatory profile induced by flagellin exposure. It includes clusters of upregulated genes related to inflammation that are linked to a sustainable gain in chromatin accessibility and with an increased activity of specific transcription factors (TFs) whose binding may drive this process. In summary, we demonstrated that flagellin exposure induced changes in chromatin condensation in BECs, which sustains the reprogramming of transcriptional patterns.

支气管上皮细胞的表观基因组景观揭示了训练免疫的建立。
先天免疫记忆,又称训练免疫,是指先天免疫细胞在短暂的刺激后获得记忆特征,从而在继发性远程攻击时产生非特异性修饰性炎症反应的能力。支气管上皮细胞(BECs)参与先天免疫防御,是下呼吸道遇到吸入病原体的第一个细胞。我们最近发现,BECs通过表观遗传机制在预先暴露于铜绿假单胞菌鞭毛蛋白后具有先天免疫记忆能力。在本研究中,我们通过鞭毛蛋白预暴露诱导染色质结构的修饰,从而导致随后基因表达的变化来研究这种机制。通过一种无监督的方法来联合分析染色质可及性和基因表达,我们绘制了BECs记忆建立过程中表观基因组和转录组谱的重塑图谱。我们确定了鞭毛蛋白暴露诱导的记忆调节谱。它包括与炎症相关的上调基因簇,这些基因簇与染色质可及性的持续增加和特定转录因子(tf)活性的增加有关,其结合可能推动这一过程。总之,我们证明了鞭毛蛋白暴露诱导BECs中染色质凝聚的变化,这维持了转录模式的重编程。
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
Genes and immunity
Genes and immunity 医学-免疫学
CiteScore
8.90
自引率
4.00%
发文量
28
审稿时长
6-12 weeks
期刊介绍: Genes & Immunity emphasizes studies investigating how genetic, genomic and functional variations affect immune cells and the immune system, and associated processes in the regulation of health and disease. It further highlights articles on the transcriptional and posttranslational control of gene products involved in signaling pathways regulating immune cells, and protective and destructive immune responses.
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