m6 一个mRNA修改增强了Th17的功能,激发了自身免疫
Xuefei Wang1,2, Chen Chen3,4, Hongwei Sun5
1Department of Geriatrics, Medical Center on Aging of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. wangxf@shsmu.edu.cn.
Science China. Life sciences
|July 5, 2023
概括
编写METTL3的m6A对T助手17 (Th17) 细胞的分化和功能至关重要. 缺乏METTL3会损害Th17细胞,降低自身免疫性疾病的严重程度.
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.
- 分子生物学分子生物学
背景情况:
- 甲基氨酸 (m6A) 是最常见的RNA修饰,影响基因表达和细胞过程.
- 已知METTL3,一个m6甲基转移酶,可以调节T细胞恒温和调节T细胞功能.
- 对于免疫和自身免疫至关重要的T辅助17 (Th17) 细胞中METTL3的作用仍然在很大程度上未被探索.
研究的目的:
- 研究METTL3在Th17细胞分化中的功能及其在自身免疫性疾病中的作用.
- 阐明METTL3调节Th17细胞活动的分子机制.
主要方法:
- 产生Mettl3f/fIl17aCre小鼠,以便在Th17细胞中有条件删除METTL3.
- 评估Th17细胞分化和实验性自身免疫脑膜炎 (EAE) 的发展.
- 在Th17细胞中分析IL-17A,CCR5和SOCS3mRNA的表达和稳定性.
主要成果:
- 在T细胞中METTL3缺乏严重损害了Th17细胞分化.
- Mettl3f/fIl17aCre小鼠表现出EAE严重性降低和Th17细胞透到中枢神经系统 (CNS) 的减少.
- 通过增强SOCS3mRNA稳定性,METTL3枯竭减弱了IL-17A和CCR5的表达,破坏了Th17细胞的功能.
结论:
- 由METTL3介导的修饰对于维持Th17细胞功能至关重要.
- METTL3在Th17细胞介导的自身免疫疾病 (如EAE) 的发病过程中发挥着重要作用.
- 向METTL3为Th17细胞驱动的自身免疫疾病提供了潜在的治疗策略.
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