痕信号驱动小鼠和非人类灵长类动物的肠道移植与宿主疾病
Victor Tkachev1,2,3,4, Ashley Vanderbeck5,6, Eric Perkey5,7
1Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA 02114, USA.
Science translational medicine
|June 28, 2023
概括
通过减少T细胞透,DLL4-Notch阻塞改善了存活率,并通过减少移植后的肠道移植与宿主疾病 (GVHD). 这种保存机制针对肠道GVHD的一个关键途径.
科学领域:
- 免疫学 免疫学 免疫学
- 移植生物学 移植生物学
- 细胞信号传递 细胞信号传递
背景情况:
- 缺口信号,特别是涉及DLL4,驱动T细胞致病性和移植对宿主疾病 (GVHD) 后异构造血细胞移植 (allo-HCT).
- 了解保存机制并确定Notch信号的抑制策略对于改善allo-HCT结果至关重要.
研究的目的:
- 评估抗体介导的DLL4阻断在非人类灵长类动物 (NHP) 的allo-HCT.模型中的有效性.
- 阐明DLL4封锁对T细胞行为和GVHD产生影响的机制,重点关注肠道导向.
主要方法:
- 用抗体介导的DLL4阻断在NHP合并HCT模型中进行.
- 研究了T细胞转录程序,肠道归属整合素α4β7表达和细胞连接体来源.
- 进行了跨物种的比较,以评估进化保护.
主要成果:
- 短期DLL4阻塞增强了移植后的存活率,并提供了对胃肠道GVHD的持久保护.
- DLL4阻断调节的T细胞转录程序,与肠道透和降低常规T细胞上的α4β7整蛋白表达相关.
- 二级淋巴体器官中的纤维质网状细胞被确定为DLL4连接体的关键来源,影响α4β7整体蛋白上调.
结论:
- DLL4-Notch阻塞是一种有效的策略,可以减少T细胞透到肠道,并改善调节与常规T细胞的比率.
- 这种方法表明DLL4-Notch信号传输在减轻肠道GVHD方面发挥了保留,独特和可向的作用.
相关概念视频
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
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The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
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