细菌脂 通过抑制ILC3衍生的IL-22生产来加剧结肠炎
Bin Bao1, Youyuan Wang2, Pavl Boudreau3
1Division of Gastroenterology, Hepatology, and Nutrition; Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts; Division of Infectious Diseases, Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts; School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei, Anhui, China.
来自Bacteroides fragilis的细菌脂会使肠道炎症恶化. 通过提升保护性免疫反应,在小鼠中去除这些脂素可以减少结肠炎的严重程度,突出了它们在粘膜免疫中的作用.
科学领域:
- * 胃肠道学和免疫学
- * 微生物组与宿主之间的相互作用
背景情况:
- * 由 Bacteroidetes 生产的肠道细菌脂体在毒性和宿主免疫力中起着复杂的作用.
- *在炎症性肠病 (IBD) 患者中观察到改变的脂形状.
- *细菌脂调节肠道平衡和炎症的确切机制尚未完全理解.
研究的目的:
- * 调查 Bacteroides fragilis sfingolipids 在调节肠道炎症中的作用.
- *阐明细菌脂对宿主粘膜免疫反应的影响.
主要方法:
- * 采用硫酸 (DSS) 诱导的大肠炎小鼠模型,用B. fragilis菌株单独殖民,有或没有脂.
- *采用转录,蛋白质和细胞分析,包括结肠扩展剂和有机物.
- *评估了宿主免疫细胞种群,细胞因子 (例如IL-22,IL-18),上皮STAT3活性和细胞增殖.
主要成果:
- * 被B. fragilis殖民的小鼠缺乏脂体,显著减少了DSS诱导的大肠炎的严重程度.
- * 缺少螺旋脂质与先天性淋巴细胞 (ILC3) 增加的介质素-22 (IL-22) 生产相关.
- *发现B. fragilis的脂阻碍了表皮IL-18的产生,并抑制了来自特定ILC3子集的IL-22释放.
结论:
- * B. fragilis衍生的脂酸会加剧粘膜炎症.
- *这种恶化是通过抑制上皮细胞IL-18表达而发生的.
- * 细菌脂还抑制ILLC3细胞的IL-22产生,导致肠道炎症.
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