YTHDF2/m6 A/NF-κB轴通过调节内Tregs来控制抗瘤免疫力
Linda Zhang1,2,3,4, Xiaoyang Dou1,2,3,4, Zhong Zheng1,2,3,4
1Department of Chemistry, The University of Chicago, Chicago, IL, USA.
The EMBO journal
|June 22, 2023
概括
调节性T细胞中的m6A读者YTHDF2抑制了抗瘤免疫力. 它在瘤细胞中的删除通过损害瘤微环境中的调节性T细胞功能来减少瘤生长.
科学领域:
- 免疫学 免疫学 免疫学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 癌症生物学 癌症生物学
背景情况:
- 修改mRNA的N6-甲基氨酸 (m6A) 调节了免疫细胞的功能.
- 在瘤微环境 (TME) 内的调节性T (Treg) 细胞中m6A读者YTHDF2的作用尚不清楚.
- 在TME中,Treg细胞在免疫抑制中发挥着关键作用.
研究的目的:
- 研究TME内的Treg细胞中YTHDF2的功能.
- 确定Treg细胞中YTHDF2缺失对瘤生长的影响.
- 阐明YTHDF2调节TME中Treg细胞的分子机制.
主要方法:
- 产生了在Treg细胞中具有Ythdf2缺失的小鼠.
- 在这些小鼠中分析了瘤生长和免疫细胞种群.
- 研究了YTHDF2调节Treg细胞功能的机制,包括细胞亡和抑制能力.
- 研究了瘤亡因子 (TNF) 信号传递和NF-κB通路的作用.
主要成果:
- 在Treg细胞中失去YTHDF2显著减少了小鼠的瘤生长.
- 在Treg细胞中Ythdf2丧失并没有影响周围免疫常态稳定.
- 在TME中,YTHDF2删除导致Treg细胞亡增加和抑制功能受损.
- 在TME中提升的TNF信号增加了YTHDF2的表达,这加速了编码NF-κB负调节者的m6A修饰转录的降解.
结论:
- 在Treg细胞中的YTHDF2通过在TME内保持Treg抑制功能来促进瘤生长.
- 在Treg细胞中,YTHDF2充当TNF诱导的NF-κB信号调节的关键调解者.
- 向瘤内Treg细胞中的YTHDF2代表了抗癌免疫疗法的有希望的策略,以增强抗瘤免疫反应,同时最大限度地减少周围炎症.
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