循环节电路通过维持RORγt的表观遗传配置来控制3组先天性淋巴细胞的可塑性
Bishan Bhattarai1, Alina Ulezko Antonova1, Jose L Fachi1
1Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
Nature immunology
|August 13, 2025
概括
循环蛋白REV-ERBα和REV-ERBβ对于维持肠道免疫细胞身份 (ILC3) 至关重要. 它们的缺失促进有害细胞转化,影响肠道平衡,增加感染易感性.
科学领域:
- 免疫学 免疫学 免疫学
- 时间生物学 时间生物学
- 微生物组研究的研究.
背景情况:
- 肠道平衡依赖于昼夜节律影响免疫细胞,如第三组先天性淋巴细胞 (ILC3).
- ILC3s产生IL-22用于肠道健康,但可以转化为ILC1s,可能破坏免疫平衡.
- 昼夜蛋白在调节ILC可塑性中的作用尚不清楚.
研究的目的:
- 研究日间蛋白质,特别是REV-ERBα和REV-ERBβ如何控制ILC3s的可塑性.
- 阐明这些昼夜蛋白质维持ILC3身份和功能的分子机制.
主要方法:
- 使用了在ILC中缺乏REV-ERBα和REV-ERBβ的淘汰赛小鼠模型.
- 执行单细胞多组学和基因编辑来分析细胞和分子变化.
- 进行了染色素和代谢分析,以评估调节和代谢重编程.
主要成果:
- 联合删除REV-ERBα/REV-ERBβ导致ILC3转化为ILC1,减少IL-22和增加干扰素γ的产生.
- 这些昼夜蛋白质的损失增加了对Citrobacter rodentium感染的易感性.
- 在REV-ERBα/REV-ERBβ缺乏细胞中的NFIL3上调抑制了RORγt表达,导致T-bet驱动状态.
结论:
- REV-ERBα和REV-ERBβ对于保持ILC3的身份和肠道完整性至关重要.
- 这些昼夜蛋白通过时钟基因通路调节RORγt表达,防止有害的ILC可塑性.
- 保持ILC3的身份对于抵抗肠道炎症和感染至关重要.
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