施莱芬11通过其核糖核酶活性,在检测到单链DNA时触发先天性免疫反应
Peng Zhang1, Xiaoqing Hu1, Zekun Li1
1State Key Laboratory of Common Mechanism Research for Major Diseases, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China.
Science immunology
|June 14, 2024
概括
具有CGT动机的细胞内单链DNA (ssDNA) 激活了天生的免疫力. 施莱芬11 (SLFN11) 作为RNase,分裂转移RNA (tRNA),触发细胞因子表达和细胞死亡.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 病毒学 病毒学
背景情况:
- 天生的免疫系统识别核酸.
- 细胞内单链DNA (ssDNA) 在免疫中的作用尚不清楚.
- 病原体感染和疾病增加细胞内sDNA.
研究的目的:
- 研究细胞内ssDNA如何刺激天生的免疫力.
- 确定ssDNA的模式识别受体.
- 阐明ssDNA诱导的免疫反应的机制.
主要方法:
- 研究了对ssDNA的反应中的细胞因子表达和细胞死亡.
- 确定了Schlafen 11 (SLFN11) 作为一个ssDNA结合RNase.
- 使用的小鼠模型缺乏Slfn9 (SLFN11同类).
主要成果:
- 细胞内ssDNA触发细胞因子表达和细胞死亡,这取决于CGT动机.
- SLFN11对于对ssDNA和腺相关病毒的先天性免疫反应至关重要.
- SLFN11结合含有CGT动机的ssDNA,转移到细胞质,并分裂转移RNA (tRNA).
- 缺少Slfn9的小鼠抵抗CGT ssDNA诱导的炎症和肝炎.
结论:
- CGT ssDNA 作为一个免疫刺激核酸.
- SLFN11/9是模式识别受体,激活天生的免疫力.
- DNA免疫传感与RNase激活和tRNA裂变相结合.
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