乳酸调节RNA剪接,以促进CTLA-4在瘤透调节性T细胞中的表达
Rui Ding1, Xiaoyan Yu1, Zhilin Hu2
1Hongqiao International Institute of Medicine, Tongren Hospital & Shanghai Institute of Immunology, State Key Laboratory of Systems Medicine for Cancer, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Immunity
|February 28, 2024
概括
乳酸盐通过改变调节性T细胞 (Tregs) 中的RNA剪接来影响瘤免疫力. 这一过程由USP39和Foxp3调解,增强CTLA-4的表达,影响瘤微环境中的Treg功能.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- RNA拼接在癌症的发展中起着重要作用.
- 在瘤微环境 (TME) 中,RNA剪接对宿主抗瘤免疫力的影响尚不清楚.
- 调节性T细胞 (Tregs) 在TME内的免疫抑制中至关重要.
研究的目的:
- 研究RNA拼接如何影响瘤微环境中的调节性T细胞功能.
- 阐明乳酸和特定拼接因子在调节Treg细胞活性中的作用.
- 探索RNA剪接,CTLA-4表达和结直肠癌之间的联系.
主要方法:
- 在瘤透Treg细胞中分析RNA拼接模式.
- 研究乌比基特异性酶39 (USP39) 在RNA剪接和CTLA-4表达中的作用.
- 评估乳酸对以Foxp3依赖的方式USP39介导的剪接的影响.
- 关联RNA拼接效率与Treg细胞特征和患者数据.
主要成果:
- 乳酸糖调节Foxp3依赖的RNA剪接,通过CTLA-4维持Treg细胞表型和功能.
- USP39对于RNA剪接介导的CTLA-4表达是必不可少的,控制Treg细胞功能.
- 乳酸酸促进USP39介导的RNA剪接,以依赖Foxp3的方式增强CTLA-4表达.
- 从结直肠癌患者的Treg细胞中观察到CTLA-4RNA拼接效率的提高.
结论:
- 在瘤微环境中的Treg细胞中,RNA剪接具有免疫学相关性.
- 乳酸利用USP39和Foxp3通过CTLA-4RNA拼接来调节Treg细胞功能.
- 这些发现提供了对控制Tregs中CTLA-4表达和癌症免疫力的环境机制的见解.
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