干白素-1β在人体造血原生细胞中诱导受过训练的先天免疫力 in vitro
Daniela Flores-Gomez1, Willemijn Hobo2, Diede van Ens2
1Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, Gelderland, the Netherlands.
Stem cell reports
|November 8, 2024
概括
干白素-1β (IL-1β) 暴露在体外重新编程人类造血原生细胞 (HPC),诱导训练免疫力. 这种表观遗传和代谢重编程增强了单细胞的炎症反应,并促进了动脉动脉道.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 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:
- 训练免疫是先天免疫细胞中长期存在的高反应性表型,由表观遗传和代谢重编程驱动.
- 在小鼠中,受过训练的免疫力是由BCG,β-葡萄糖或西方饮食诱导的,涉及骨髓血液造血原生细胞 (HPC) 中的互白素-1β (IL-1β) 信号传递.
研究的目的:
- 为了研究IL-1β是否可以诱导人体骨髓原始HPCs培训免疫在体外.
- 在暴露于IL-1β后,描述人类HPC及其单细胞后代的功能和转录组变化.
主要方法:
- 人类骨髓衍生HPC被暴露于IL-1β4小时.
- 随后,HPC被扩展并分化为单细胞.
- 进行了功能性测试 (殖民地形成,细胞因子产生) 和转录组分析.
主要成果:
- 暴露于IL-1β的HPC呈现出增加的颗粒细胞-巨细胞殖民地形成单元.
- 从暴露于IL-1β的HPC衍生的单细胞在用LPS和Pam3Cys.再刺激后产生了更高水平的瘤亡因子 (TNF) 和IL-1β.
- 这些单细胞表现出增强的代谢活性,并调高了关键的动脉动脉和炎症基因表达通路.
结论:
- 短暂的IL-1β体外暴露会在人类骨髓衍生的HPC中诱导受训免疫表型.
- 这种重编程增强了由此产生的单细胞的炎症潜力和代谢活性,这表明它在人类免疫反应和潜在的疾病发病过程中发挥了作用.
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