适配器分子TIRAP为托尔类受体提供了信号特异性
Tiffany Horng1, Gregory M Barton, Richard A Flavell
1Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Nature
|November 26, 2002
概括
收费类受体 (TLRs) 感知感染,激活免疫反应. 这项研究表明,适应蛋白TIRAP对于TLR4信号传输至关重要,但对于TLR5,TLR7或TLR9则不至关重要,这表明它在免疫传感中的作用不同.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 哺乳动物的托尔类受体 (TLRs) 是感染的关键传感器,启动先天性和适应性免疫反应.
- TLRs通过它们的Toll/interleukin-1受体 (TIR) 域和适应蛋白MyD88.8.通过它们发出信号.
- 虽然TLRs和IL-1受体通过MyD88发出信号,但个别受体通路不同.
研究的目的:
- 研究适配蛋白TIRAP在托尔类受体信号传递中的作用.
- 为了生成和表征缺少Tirap基因的小鼠.
主要方法:
- 一代的Tirap缺乏的小鼠.
- 对各种TLR连体 (TLR4,TLR5,TLR7,TLR9,TLR2,TLR1,TLR6) 和IL-1/IL-18.6的免疫反应的评估.
- 对细胞因子生产,NF-kappaB激活和MAPK激活的分析.
主要成果:
- 缺乏TIRAP的小鼠对TLR5,TLR7,TLR9连接体和IL-1/IL-18呈现正常反应.
- 在对LPS (TLR4连接体) 的反应中观察到细胞因子生产和NF-kappaB/MAPK激活的缺陷.
- 在Tirap缺乏的小鼠中,对TLR2,TLR1和TLR6配体的反应受损也被观察到.
结论:
- TIRAP在托尔类受体信号传递中起着差异性作用.
- TIRAP对于TLR4介导的免疫反应至关重要.
- TIRAP可能会为个人TLR下游信号的特异性做出贡献.
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