在ILC3发育过程中,mTORC2充当了mTORC1缺陷中介的障碍的守门人
Ya-Fei Deng1,2, Shu-Ting Wu1, Hong-Yan Peng1
1Pediatrics Research Institute of Hunan Province and Hunan Provincial Key Laboratory of Children's Emergency Medicine, Hunan Children's Hospital, Changsha, 410007, China.
Acta pharmacologica Sinica
|July 5, 2023
概括
拉巴胺素复合体1 (mTORC1) 的哺乳动物点对于3组先天性淋巴细胞 (ILC3) 发育和肠道免疫是至关重要的. 当mTORC1被抑制时,mTORC2可以保护ILC3s免受损失.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 第三组先天性淋巴细胞 (ILC3s) 对于肠道免疫和屏障功能至关重要.
- 哺乳动物对拉巴胺素 (mTOR) 信号传导在ILC3s中的作用正在研究中,对mTOR复合物1 (mTORC1) 和mTOR复合物2 (mTORC2) 在ILC3恒温中交叉交叉的理解有限.
研究的目的:
- 阐明mTORC1和mTORC2在调节ILC3发育,功能和肠道平衡中的特定作用.
- 研究在ILC3s中mTORC1-mTORC2交叉通话的潜在机制.
主要方法:
- 使用单细胞RNA测序来分析在mTORC1缺乏下ILC3异质性.
- 基因操纵,包括Raptor删除和Rictor淘汰,用于抑制mTORC1和调节mTORC2活动.
- 用小鼠模型来评估ILC3介导的肠道平衡和感染易感性.
主要成果:
- mTORC1,但不是mTORC2,对于ILC3发育,IL-22产生和肠道平衡至关重要.
- mTORC1 缺乏会破坏 ILC3 的异质性,导致 ILC1 样细胞的分化增加和NFIL3 表达的减少.
- IL-23在ILC3中激活mTORC1和mTORC2;然而,mTORC1的抑制增强了mTORC2的活性,这通常被S6K介导的Rictor酸化抑制.
- 同时抑制mTORC1和逆转mTORC2过活性的ILC3s导致严重的细胞损失和完全易受肠道感染.
结论:
- mTORC1作为ILC3异质性和发展的关键调节器.
- 当mTORC1活动受到损害时,mTORC2在肠道感染期间对ILC3s进行细胞损失和免疫功能障碍的保护作用.
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