Bacteroides fragilis毒素抑制METTL3-介导的m6A修改巨细胞促进炎症性肠病
Yuqing Yan1, Li Tian2, Ying Zhao1
1State Key Laboratory of Systems Medicine for Cancer, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute, Shanghai, China.
Journal of Crohn's & colitis
|March 11, 2025
概括
细菌脆毒素 (BFT) 通过降低METTL3和增加ITGA5表达来降低炎症性巨细胞中的N6-甲基氨酸 (m6A) 修饰,从而影响炎症性肠病.
科学领域:
- 微生物学和免疫学
- 史诗转录组学 史诗转录组学
- 胃肠病学 胃肠病学
背景情况:
- 肠毒性细菌菌 (ETBF) 产生细菌菌毒素 (BFT),这是ETBF诱导的大肠炎的关键因素.
- 炎症性巨细胞与炎症性肠病 (IBD) 的病原发生有关.
研究的目的:
- 研究BFT对宿主mRNAN6-甲基氨酸 (m6A) 修饰在炎症巨细胞中的影响.
- 阐明BFT诱导的m6A变化背后的机制及其在结肠炎中的作用.
主要方法:
- 单细胞测序用于在IBD和大肠炎模型中识别细胞类型.
- 使用了一个缺乏bft基因 (ETBF[Δbft]) 的ETBF菌株.
- 在体外和体内实验中探索BFT对m6A修饰和基因表达的影响.
主要成果:
- 炎症性巨细胞在ETBF相关的大肠炎中得到丰富,并由ETBF激活.
- 通过通过FOXD3.3抑制METTL3转录,BFT减少了巨细胞中的m6A修饰.
- 通过减少YTHDF2介导的mRNA降解,BFT通过调节ITGA5表达.
- 在小鼠模型中,用Cilengitide向ITGA5改善了结肠炎.
结论:
- 在巨细胞中,BFT会破坏m6A表达体,降低METTL3并促进ITGA5的表达.
- 这些发现突显了肠道微生物群介导的m6A调节在IBD病变发生过程中的作用.
- BFT对巨细胞的影响为炎症性肠病提供了潜在的治疗点.
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