系统性扰动屏幕识别了炎症性巨细胞状态的调节者以及TNF mRNA m6A修饰的作用
Simone M Haag1, Shiqi Xie1, Celine Eidenschenk1
1Genentech Inc., South San Francisco, CA, USA.
Nature genetics
|October 24, 2024
概括
研究人员发现了巨细胞在慢性炎症期间如何发展炎症状态. 他们发现,阻断N6-甲基氨酸 (m6A) 对TNF转录的修改增强了mRNA稳定性和瘤坏死因子 (TNF) 生产,影响了天生的免疫力.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 基因组学就是基因组学.
背景情况:
- 巨细胞对于组织平衡至关重要,并表现出可塑性.
- 慢性炎症涉及持续的炎症性巨细胞状态,有助于疾病.
- 驱动这些炎症状态的调节机制尚不清楚.
研究的目的:
- 系统地识别控制巨细胞炎症状态的调节回路.
- 揭示导致持续炎症性巨细胞表型的产生背后的机制.
主要方法:
- 在初级小鼠巨细胞中进行全基因组表型查.
- 在人类原发性巨细胞中转录和细胞因子对遗传干扰的分析.
- 功能性基因组学方法结合了体内和体外研究.
主要成果:
- 确定了五种不同的巨细胞炎症状态的调节者.
- 丢失N6-甲基亚诺辛 (m6A) 写作元件取消了TNF转录的m6A修改.
- 在m6A写字器丢失后,观察到增强的TNFmRNA稳定性和产生.
结论:
- 表型特征揭示了不同巨细胞炎症状态的调节电路.
- 转录后控制TNFmRNA稳定性是天生的免疫的一个关键机制.
- m6A修饰调节TNF的产生和炎症反应.
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