对调控性T细胞中转录因子Foxp3表达的时间和上下文依赖的要求
Wei Hu1,2, Gabriel A Dolsten3, Eric Y Wang4,5,6
1Howard Hughes Medical Institute and Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA. wei.hu.wh447@yale.edu.
Nature immunology
|October 8, 2025
概括
调节性T (Treg) 细胞需要Foxp3进行初始发育,但成熟的Treg细胞对其损失有弹性. Foxp3 在炎症和瘤免疫力中至关重要.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 通过Foxp3表达定义的调节性T (Treg) 细胞对于免疫恒温至关重要.
- 通过Foxp3调节Treg转录网络的精确机制尚未完全阐明.
研究的目的:
- 在各种条件下调查Foxp3在Treg细胞功能和转录程序中的作用.
- 探索Treg细胞中对Foxp3的上下文依赖性要求.
主要方法:
- 利用一种新的化学遗传系统在体内诱导Foxp3蛋白质降解.
- 在不同的生理和病理环境下,在Foxp3损失后评估Treg细胞的转录和功能变化.
主要成果:
- 福克斯p3对于建立新生成的Treg细胞程序至关重要,但成熟的Treg细胞在稳定状态条件下表现出对其损失的弹性.
- 严重的炎症加剧了Foxp3损失对Treg细胞转录组和健康状况的影响.
- 瘤Treg细胞对Foxp3降解高度敏感,导致抑制功能受损和瘤缩.
结论:
- 在Treg细胞中对Foxp3的要求取决于环境,根据细胞成熟度,炎症状态和瘤微环境而有所不同.
- 在Treg细胞中准Foxp3为癌症免疫治疗提供了潜在的治疗策略.
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