一个由代谢物触发的细胞-ILC2电路驱动小肠的重塑
Christoph Schneider1, Claire E O'Leary1, Jakob von Moltke1
1Department of Medicine, University of California San Francisco (UCSF), San Francisco, CA 94143, USA.
Cell
|June 12, 2018
概括
小肠细胞-ILC2回路通过重新塑造肠道来应对寄生虫. 这个由A20调节的电路使用酸感应来预防新的虫感染.
科学领域:
- 免疫学
- 胃肠病学
- 微生物学
背景情况:
- 小肠细胞-ILC2循环对于表皮对肠道寄生虫的反应至关重要.
- 细胞感知病原体并通过IL-25激活2型先天性淋巴细胞 (ILC2).
- ILC2s表达IL-25受体,由A20 (Tnfaip3) 负调节.
研究的目的:
- 研究A20在调节细胞-ILC2电路中的作用.
- 阐明这种电路调节肠道重塑和免疫的机制.
- 为了识别参与电路激活的代谢信号.
主要方法:
- 在ILC2中对A20进行基因操纵.
- 对小肠形态和免疫细胞群的分析.
- 肠道光线的代谢分析.
- 使用特定代谢物和受体抗剂的功能测试.
主要成果:
- 在ILC2s中A20缺乏会自发地激活细胞-ILC2电路,导致小肠延长和重塑.
- 电路的激活与原生体Tritrichomonas的断奶和殖民有关,这增加了光酸盐.
- 酸盐通过TRPM5和IL-25依赖的途径激活ILC2.
- 这种重塑赋予了对二次虫感染的抵抗力,模仿了同时存在的免疫力.
结论:
- 一个涉及细胞和ILC2s的代谢传感电路调节肠道适应和免疫力.
- 酸盐作为激活这一循环的关键代谢物.
- 状细胞-ILC2酸轴提供了对新虫感染的抵抗力,这表明一种用于管理光线病友生物的进化机制.
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