沃戈宁通过激活AhR通路来改善结肠炎,以调节ILC3/ILC1的可塑性
Qiujuan Ye1, Shaowei Huang2, Ying Wang2
1Department of Gastroenterology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, PR China.
沃贡尼通过激活基碳化合物受体 (AhR) 来调节先天性淋巴细胞可塑性来治疗炎症性肠病 (IBD). 这种天然化合物还调节肠道微生物群的代谢物,为IBD提供了一种新的治疗方法.
科学领域:
- 免疫学 免疫学 免疫学
- 胃肠病学 胃肠病学
- 药理学 药理学是指药理学的学科.
背景情况:
- 炎症性肠病 (IBD) 的特征是肠壁功能障碍,原因是3组先天性淋巴细胞 (ILC3) 和1组先天性淋巴细胞 (ILC1) 之间的不平衡.
- 基碳化合物受体 (AhR) 信号传递对于维持ILC3/ILC1平衡至关重要.
- 黄,一种黄类化合物,显示出在IBD中修复肠损伤的潜力,但其涉及AhR和ILC可塑性的机制尚未完全理解.
研究的目的:
- 为了研究沃贡宁对IBD的免疫调节作用.
- 阐明沃贡因的潜在机制,重点关注AhR通路激活和ILC3/ILC1可塑性,在体外和体内.
主要方法:
- 在使用DSS治疗的小鼠中诱导慢性结肠炎,与沃贡尼和AhR抗剂 (CH223191) 治疗.
- 结肠组织分析了他的病理学,上皮屏障功能,AhR激活和ILC可塑性.
- 使用16S测序和非向代谢学分析了肠道微生物群和代谢物.
- 试验室内实验包括细胞培养和CETSA试验,以确认分子机制.
主要成果:
- 沃贡尼改善了结肠损伤,减少了炎症,并在结肠炎模型中增强了紧接口蛋白.
- 沃贡因阻止了ILC3转化为ILC1,这种效应被AhR抗剂逆转.
- 沃戈宁改变了肠道微生物群以产生AhR配体 (氨酸,1H--3-甲) 并在体外直接与AhR结合.
- 在体外,wogonin治疗增加了表皮屏障功能标记物 (Occludin,Claudin1).
结论:
- 沃戈宁通过调节ILC3/ILC1可塑性,有效改善DSS诱导慢性结肠炎的结果.
- 沃戈宁直接与AhR结合,并通过调节肠道微生物群的托代谢来间接激活AhR通路.
- 沃贡因通过向AhR通路和肠道微生物群,代表了IBD的有希望的治疗剂.
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