在小鼠模型中,LSD1驱动肠上皮质成熟,并控制小肠免疫细胞组成,独立于微生物群
Alberto Díez-Sánchez1, Håvard T Lindholm2,3, Pia M Vornewald2
1Centre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway. alberto.d.sanchez@ntnu.no.
Nature communications
|April 22, 2024
概括
成熟的肠上皮,由氨酸特异性脱甲基酶1A (LSD1) 调节,对于肠道平衡至关重要. LSD1控制上皮细胞的发育和免疫细胞的组成,影响肠道健康.
科学领域:
- 胃肠病学 胃肠病学
- 免疫学 免疫学 免疫学
- 发展生物学 发展生物学
背景情况:
- 产后肠道发育涉及微生物群,免疫耐受性和上皮质成熟.
- 微生物群,免疫细胞和上皮之间的相互作用尚未完全理解.
- 成熟的肠表皮在这个过程中的特定作用仍然在很大程度上是未知的.
研究的目的:
- 研究氨酸特异性脱甲酶1A (LSD1) 在肠上皮质成熟中的作用.
- 确定LSD1控制的上皮发育如何影响肠道免疫微环境.
- 阐明表皮细胞调节免疫细胞种群的机制.
主要方法:
- 使用了微生物群枯竭的小鼠模型.
- 评估了肠表皮特异性LSD1表达对表皮成熟的影响.
- 分析了免疫细胞群的组成 (血细胞,ILCs,骨髓细胞).
- 测量了表皮质衍生化基因的表达,包括Cxcl16.
主要成果:
- 肠表皮内在的LSD1对于产后表皮的成熟和维护至关重要.
- 这种LSD1依赖的上皮质成熟会影响血细胞,先天性淋巴细胞 (ILC) 和特定的髓状细胞群.
- LSD1调节了像Cxcl16这样的上皮化基因的表达,调节了与免疫细胞的交叉通话.
- 这种机制特别影响本地ILC2s,但不影响ILC3s.
结论:
- 成熟的肠表皮在调节局部免疫细胞组成方面发挥着主导作用.
- LSD1是表皮质成熟的关键调节者,它对肠道免疫有影响.
- 皮质衍生化基因是皮质-免疫细胞相互作用的关键调解者.
- 这些发现凸显了表皮发育在维持肠道平衡中的重要性.
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