河马/Mst信号对 CD8α+树突细胞的代谢状态和免疫功能
Xingrong Du1, Jing Wen1, Yanyan Wang1
1Department of Immunology, St Jude Children's Research Hospital, Memphis, TN, USA.
Nature
|June 1, 2018
概括
河马通路的Mst1和Mst2 (Mst1/2) 选择性地编程CD8α+树突细胞的功能和代谢. Mst1/2对于CD8α+树突细胞至关重要
科学领域:
- 免疫学
- 细胞生物学
- 系统生物学
背景情况:
- 树突细胞 (DCs) 是先天性和适应性免疫的关键调节者.
- CD8α+ DC对CD8+ T细胞呈现抗原,对抗病毒,抗菌和抗瘤反应至关重要.
- 控制CD8α+DC功能和代谢调节的分子通路在很大程度上仍未被描述.
研究的目的:
- 确定CD8α+树突细胞功能和新陈代谢的分子调节剂.
- 研究Hippo路径在CD8α+DC子集专业化中的作用.
主要方法:
- 使用数据驱动的系统生物学算法 (NetBID) 进行路径分析.
- 生成了树突细胞特异性的Mst1/2淘汰小鼠模型.
- 评估了T细胞原始化,抗瘤免疫力,细胞代谢和细胞因子的产生.
主要成果:
- 在NetBID分析中发现CD8α+DC中的Hippo通路激酶活性增强.
- 干细胞特异性Mst1/ 2的删除破坏了CD8+T细胞平衡和抗瘤免疫力.
- 缺乏Mst1/ 2的CD8α+细胞表现出抗原表达受损和氧化代谢发生变化.
- Mst1/2信号对CD8α+DC生物能,线粒体动力学和IL-12产生至关重要.
结论:
- Mst1/ 2被确定为CD8α+树突细胞功能的选择性驱动因素.
- 在CD8α+ DC中整合代谢活动和细胞因子信号.
- 免疫信号和新陈代谢重编程的相互作用是唯一的DC子集功能.
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