TASL是通过TLR7-9激活IRF5的SLC15A4相关适配器
Leonhard X Heinz1, JangEun Lee2, Utkarsh Kapoor1
1CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
Nature
|May 21, 2020
概括
研究人员发现了一种新的蛋白质TASL, TASL将内分泌体的托尔类受体 (TLR) 与IRF5激活联系在一起,这解释了它在全身性红斑狼中的作用.
科学领域:
- 免疫学
- 分子生物学
- 遗传学
背景情况:
- 托尔类受体 (TLR) 对于病原体的识别和免疫反应的启动至关重要.
- 系统性红斑狼 (SLE) 与遗传因素和免疫系统失调有关.
- SLC15A4 是一种内解体TLR机械元件,与自身免疫性疾病有关.
研究的目的:
- 描述由CXorf21编码的新型蛋白质及其在内溶性TLR信号传递中的作用.
- 阐明CXorf21,SLC15A4和天生的免疫反应之间的相互作用.
- 了解与这些成分相关的SLE病变的分子机制.
主要方法:
- 蛋白相互作用研究以确定SLC15A4的结合伙伴.
- 在人类免疫细胞中删除基因和突变,以评估蛋白质功能.
- 在TLR激动剂刺激时下游信号通路 (IRF,NF-κB,MAPK) 的分析.
主要成果:
- 一种新的蛋白质TASL (TLR适配器与溶酶体上的SLC15A4相互作用) 被确定.
- TASL与SLC15A4相互作用,对内溶性TLR反应至关重要.
- 通过pLxIS动机,TASL专门调解IRF通路的激活,将TLR7/8/9与IRF5联系起来.
结论:
- TASL作为内解体TLRs (TLR7,TLR8,TLR9) 的一个关键的先天性免疫适应体.
- 这种TASL- SLC15A4相互作用对TASL局部化和免疫信号的功能至关重要.
- 这一发现提供了内解体TLR信号组件和全身性红斑狼之间的机制联系.
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