在巨细胞中抑制METTL3可通过通过上调IRAKM调节来增强M2极化来缓解大肠炎
Yang Zhang1,2, Xin Wang1,2, Shan Cao1,2
1Department of Gastroenterology, Peking University People's Hospital, Beijing, China.
概括
甲基转移酶类3 (METTL3) 调节巨细胞两极分化和肠道炎症. METTL3缺乏通过增加IRAKM促进M2巨细胞的激活,抑制炎症,并为结肠炎提供潜在的治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 胃肠病学 胃肠病学
背景情况:
- N6-甲基氨酸 (m6A) 是一种普遍存在的RNA修饰,对巨细胞稳态和肠道免疫至关重要.
- 在肠道炎症期间,甲基转移酶类3 (METTL3) 表达在巨细胞中升高.
- 将METTL3与结肠炎联系在一起的确切机制在很大程度上仍未被探索.
研究的目的:
- 研究METTL3介导的巨细胞激活在结肠炎的作用.
- 阐明METTL3影响巨细胞极化和肠道炎症的分子机制.
主要方法:
- 建立了硫酸 (DSS) 诱导的实验性结肠炎模型.
- 使用条件淘汰赛小鼠对髓状细胞中的METTL3 (Mettl3fl/flLyz2Cre) 和髓状细胞中的IRAKM (Irakmfl/flLyz2Cre).
- 通过疾病活动指数,结肠长度和组织病理学评估结肠炎的严重程度;采用流细胞计,西部斑,qPCR和RNA-seq进行机械分析.
主要成果:
- 在髓状细胞中METTL3的有条件淘汰减弱了DSS诱导的大肠炎.
- 删除METTL3促进了M2巨细胞的两极分化,并增加了IRAKM水平,这是TLR4信号的负调节器.
- METTL3缺乏抑制了TLR信号介导的巨细胞激活,而IRAKM缺失加剧了结肠炎并促进了M1巨细胞的两极分化.
结论:
- 在肠道炎症中,METTL3-IRAKM信号对调节巨细胞两极分化至关重要.
- 这一途径代表了治疗结肠炎的潜在治疗标.
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