TOX通过转录和表观遗传编程CD8+T细胞的耗尽
Omar Khan1,2,3,4, Josephine R Giles1,2,3, Sierra McDonald5,6,7
1Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Nature
|June 18, 2019
概括
转录因子TOX对于耗尽的CD8+T (Tex) 细胞的发展至关重要,这些细胞是癌症和慢性感染的关键标. 它的缺失阻止了Tex细胞的形成,突出了TOX作为Tex细胞衰竭的关键调节者.
科学领域:
- 免疫学
- 分子生物学
- 细胞生物学
背景情况:
- 耗尽的CD8+T (Tex) 细胞表现出受损的效应器功能和不同的表观遗传和转录特征.
- 在慢性感染和癌症中,Tex细胞是免疫治疗的关键点.
- 驱动Tex细胞转录和表观遗传发育的机制尚不清楚.
研究的目的:
- 确定Tex细胞发育的关键调节者.
- 阐明转录因子在建立Tex细胞表型中的作用.
主要方法:
- 在小鼠模型中分析CD8+T细胞子集 (Tex,Teff,Tmem).
- 研究了HMG盒转录因子TOX在Tex细胞发育中的作用.
- 使用分子和表观遗传分析来描述Tex细胞编程.
主要成果:
- 确定TOX是小鼠Tex细胞形成不可或缺的中心调节剂.
- TOX由氨酸/NFAT2诱导,并在Tex细胞中以持续的,氨酸独立的前进循环运作.
- TOX为Tex细胞的承诺编排了一个独特的转录和表观遗传程序.
结论:
- TOX是Tex细胞命运的关键决定因素,它将持续的刺激转化为疲劳.
- 了解TOX的作用提供了针对Tex细胞的治疗益处的见解.
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