USP3在诱导先天免疫耐受性方面发挥着至关重要的作用
Tianhao Duan1,2,3, Yanchun Feng2, Yang Du1,2,3
1Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
EMBO reports
|November 16, 2023
概括
乌比基因特异蛋白酶3 (USP3) 通过使MyD88成为一个关键的信号分子,从而建立先天的免疫耐受性. 这种非转录的反机制调节NF-κB信号传递和先天免疫记忆.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 脂聚糖 (LPS) 支持天生的免疫力,但可以诱导耐受性,抑制NF-κB信号传递.
- 天生的免疫记忆涉及表观遗传和转录性变化,但对后翻译性调节的理解较少.
研究的目的:
- 研究翻译后调节在先天免疫耐受性中的作用.
- 确定MyD88-NF-κB信号通路中的新机制.
主要方法:
- 在LPS诱导的先天免疫反应中研究了泛素特异蛋白酶3 (USP3).
- 分析了USP3稳定,核出口以及与MyD88.8的相互作用.
- 评估了USP3对NF-κB信号和TLR/IL1β激活的影响.
主要成果:
- 在NF-κB激活时,USP3被稳定并转移到细胞质.
- 细胞质USP3从MyD88中去除了与K63结合的多比基因链,抑制了TLR/IL1β信号传递.
- LPS初始化增强了USP3细胞质转移,在二次挑战时促进了NF-κB的快速关闭.
结论:
- USP3通过非转录反来建立先天的免疫耐受性.
- MyD88-USP3轴代表了一种对先天免疫记忆至关重要的新型后翻译调节循环.
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