细胞骨预应力调节RIG-I介导的先天免疫力
Arpan Roy1, Sydney Sarver1, Jarod Beights2,3
1School of Mechanical, Aerospace, and Materials Engineering, Southern Illinois University Carbondale, Carbondale, IL 62901, USA.
概括
细胞硬度调节天生的免疫力. 软表面的细胞显示出由于细胞骨前压力影响RIG-I信号的抗病毒反应减少,而硬表面则增强了RIG-I信号.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 生物物理学的生物物理.
背景情况:
- 天生的免疫力通过信号通路提供关键的抗病毒防御,例如视网膜酸诱导基因I (RIG-I).
- 细胞骨前压力对RIG-I信号传递和先天免疫的影响,这是细胞机械传递的一个关键方面,尚不清楚.
研究的目的:
- 研究细胞骨前压力在调节RIG-I信号和I型干扰素 (IFN) 基因表达中的作用.
- 为了确定基质刚性如何影响先天免疫反应.
主要方法:
- 细胞在软 (0.6 kPa) 和硬 (8.5 kPa) 基板上培养,以改变细胞的引力和前压力.
- 聚I:C),一种病毒的dsRNA模仿,用于刺激RIG-I通路.
- 测量了IFN-β1和IFN刺激基因 (ISG) 的表达.
- 评估了TANK结合激酶1 (TBK1) 和Yes相关蛋白 (YAP) 的激活和局部化.
主要成果:
- 软基板上的细胞表现出最小的RIG-I信号激活和低的IFN-β1和ISG表达.
- 在软基质上,YAP局部化到细胞质,抑制TBK1的激活.
- 硬基板上的细胞显示RIG-I信号增强,TBK1激活升高,由于核YAP定位,IFN和ISG表达增加.
结论:
- 细胞骨前压力显著影响RIG-I信号的激活和随后的先天免疫反应.
- 基质刚性通过调节细胞骨前压力和YAP局部化,作为抗病毒信号的关键生物物理调节器.
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