巨衍生的VISTA与LRIG1相互作用,并阻碍肠道上皮的修复
Mengyuan Li1, Binfeng Chen1, Zhixiong Wang2
1Department of Rheumatology and Clinical Immunology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Cellular & molecular immunology
|August 29, 2025
概括
在巨细胞上使用的V域免疫球蛋白域激活抑制剂 (VISTA) 通过破坏肠道细胞使结肠炎恶化. 阻断VISTA或准VISTA/ LRIG1通路可以促进炎症性肠病 (IBD) 的愈合.
科学领域:
- 免疫学
- 胃肠病学
- 细胞生物学
背景情况:
- 肠上皮屏障的破坏和修复障碍是大肠炎发展的关键因素.
- 作为一个免疫检查点蛋白,V- 域免疫球蛋白抑制T细胞激活 (VISTA) 是一种免疫检查点蛋白.
- 在炎症性肠病 (IBD) 和酸 (DSS) 诱导的结肠炎模型中,VISTA在巨细胞上升调节.
研究的目的:
- 调查VISTA在结肠炎发病过程中的作用.
- 探索针对VISTA途径在IBD中的治疗潜力.
主要方法:
- 在IBD患者和DSS诱导的大肠炎小鼠模型中研究VISTA表达.
- 使用VISTA缺乏 (Vsir-/-) 和野生型 (WT) 鼠标,包括Rag1-/-.
- 进行了巨细胞消耗和转移实验.
- 研究了VISTA,LRIG1和PPARα在肠道干细胞和器官中的相互作用.
主要成果:
- 维斯塔缺乏或阻塞改善了DSS诱导的大肠炎的严重程度.
- 在VISTA缺乏的小鼠中,上皮损伤减少,巨细胞枯竭使疾病严重程度的差异正常化.
- 发现来自巨细胞的VISTA会调解上皮损伤,而VISTA缺乏会加速粘膜再生.
- 在肠道干细胞中与LRIG1相互作用,抑制PPARα,损害器官生长,增加上皮损伤.
结论:
- 巨衍生VISTA在结肠炎期间的上皮损伤中起病原作用.
- 针对VISTA/LRIG1轴是一个促进IBD上皮质修复的潜在治疗策略.
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