神经神经胺U刺激先天性淋巴细胞和2型炎症
Christoph S N Klose1, Tanel Mahlakõiv1, Jesper B Moeller1,2
1Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, New York 10021, USA.
Nature
|September 5, 2017
概括
来自神经元的Neuromedin U (NMU) 通过NMUR1激活2组先天性淋巴细胞 (ILC2). 这促进了对抗寄生虫和组织修复至关重要的2型免疫反应.
科学领域:
- 免疫学
- 神经科学
- 胃肠病学
背景情况:
- 2型细胞因子 (IL-4,IL-5,IL-9,IL-13) 对于对虫的免疫,过敏性炎症和组织修复至关重要.
- 2组先天性淋巴细胞 (ILC2) 是2型细胞因子的关键生产者,但外界刺激对ILC2反应的调节尚不清楚.
研究的目的:
- 通过神经元信号调节ILC2反应.
- 确定神经美丁U (NMU) 和其受体 (NMUR1) 在ILC2激活和功能中的作用.
主要方法:
- 在小鼠肠道中研究ILC2s和胆固醇神经元的同定位.
- 用NMU进行ILC2s的体外刺激.
- 在小鼠体内使用NMU.
- 对Nmur1缺乏的小鼠和采用细胞转移实验的分析.
主要成果:
- ILC2s选择性地表达NMU受体1 (NMUR1) 并与表达NMU的神经元共定位.
- NMU刺激激活ILC2s,诱导IL-5,IL-9和IL-13的增殖和分泌.
- 在体内使用NMU可促进2型细胞因子反应,ILC2激活,乙氨基细胞招募,寄生虫驱逐和肺炎.
- 缺乏Nmur1导致虫负担增加,证实了NMU-NMUR1轴的作用.
结论:
- NMU-NMUR1信号通路代表了肠道神经系统与先天免疫系统之间的新联系.
- 这种神经回路选择性地激活ILC2s,在粘膜部位协调快速的2型免疫反应.
- 这些反应有助于抗微生物防御,炎症和组织保护.
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