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克里斯普尔屏幕揭示了依赖营养的溶酶体和线粒体节点,影响肠道组织-居民记忆CD8⁺ T细胞形成

Jana L Raynor¹, Nicholas Collins², Hao Shi¹

¹Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

|October 15, 2024

概括

营养物质的可用性和器官信号通过控制CD8+组织居民记忆T细胞 (TRM) 发育来调节组织免疫力. 这项研究揭示了线粒体和溶解体如何受到营养素的影响,塑造TRM细胞功能和保护性反应.

科学领域:

免疫学免疫学免疫学
细胞生物学细胞生物学
代谢过程中的代谢.

背景情况:

组织稳态和细胞命运受营养的可用性和器官生物学的影响.
这些过程对组织免疫的编排,特别是CD8+组织内存T细胞 (TRM) 中的编排,尚不清楚.

研究的目的:

研究有机体信号传导和代谢途径在CD8+TRM细胞发育中的作用.
确定调节组织中TRM细胞形成和功能的营养感应机制.

主要方法:

在体内进行CRISPR-Cas9查,以确定TRM细胞发育的遗传调节者.
分析涉及营养感应的线粒体和 lysosomal 途径.
基因相互作用查,以揭示基因之间的协同或对抗关系.

主要成果:

TRM细胞的发育需要线粒体翻译和呼吸.
溶解体营养感应通路 (Flcn,Ragulator,Rag GTPases) 抑制肠道TRM细胞的形成.
这些通路或氨基酸的耗尽会激活Tfeb,将营养应激与TRM细胞编程联系起来.
缺乏Flcn会增强小肠中保护性TRM细胞的反应.
Flcn-Tfeb轴调节CCR9和TGF-β信号,影响TRM细胞迁移和分化.
线粒体蛋白Mrpl52和Acss1对早期TRM细胞的形成和在溶酶体应激下的发育至关重要.

结论:

营养素的可用性和器官信号是组织免疫的关键决定因素.
线粒体功能,溶酶体营养感应和代谢适应之间的相互作用塑造了CD8+TRM细胞的发育和功能.
针对这些途径可能提供策略来调节组织居民免疫反应.

关键词:

在CD8 T细胞中,CD8 T细胞适应性免疫是一种适应性免疫.通过饮食干预进行食干预.免疫代谢的免疫代谢.lysosome 溶解酶体是如何形成的线粒体中的线粒体.组织内存是组织内存.

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