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在天生的免疫耐受性中,TREM2 调节突触的微细胞化

Jian Meng¹, Linkun Han¹, Hui Xu¹

¹Xiamen Key Laboratory of Brain Center, The First Affiliated Hospital of Xiamen University, and Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China.

International immunopharmacology

|December 26, 2023

概括

微细胞在突触细胞分裂中表现出免疫耐受性,这是对大脑健康至关重要的过程. 在骨髓细胞2 (TREM2) 上表达的触发受体对于这种微质免疫记忆至关重要.

科学领域:

神经免疫学神经免疫学
天生免疫记忆天生的免疫记忆
微质功能微质功能

背景情况:

天生的免疫细胞,包括微质细胞,表现出免疫记忆.
微质细胞,大脑的常驻免疫细胞,调节炎症和细胞消化.
在微质细胞化和记忆中,质细胞2 (TREM2) 上表达的触发受体的作用在很大程度上是未知的.

研究的目的:

为了调查微质细胞是否表现出与细胞分裂相关的先天免疫记忆.
确定TREM2在微质先天免疫记忆中的作用.
探索TREM2参与微质免疫耐受性背后的机制.

主要方法:

周围脂多糖体 (LPS) 注射用于诱导野生型 (WT) 和Trem2淘汰赛 (Trem2 KO) 小鼠的微质激活和免疫耐受性.
研究人员量化了海马炎症标志物 (Tnfα,Il-1β) 和突触的微质细胞灭菌.
分析了微质形态和转录变化 (RNA-seq).

主要成果:

无论是WT和Trem2 KO小鼠,都显示出炎症标志物的初始增加,随后下降,表明耐受性,基因型之间没有显著差异.
在两种基因型中,单次LPS暴露促进了微质突触的细胞分解和激活.
在WT小鼠中,重复的LPS暴露减少了突触细胞分裂,并逆转了微质激活,但在Trem2 KO小鼠中没有,突出了TREM2在细胞耐受性中的作用.
在免疫耐受性期间,TREM2 缺陷改变了补充和细胞通路的转录格局.

结论:

微质表现出与突触细胞分裂相关的免疫耐受性.
在建立微质免疫耐受性方面,TREM2发挥着至关重要的作用,可能通过调节补体和细胞相关基因表达来实现.
这些发现揭示了微质和TREM2在脑免疫记忆中的新功能.

关键词:

补充系统的补充系统.天生的免疫耐受性天生的免疫耐受性.微质细胞中的微质细胞突触的消化细胞.在TREM2中,我们可以使用TREM2.

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