巨细胞吸收无细胞圆形RNA的途径
Laura Amaya1, Brian Abe2, Jie Liu3
1Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Molecular cell
|May 18, 2024
概括
细胞外循环RNAs (circRNAs) 被人类髓状细胞和B细胞吸收,影响免疫反应. 巨食肉受体和mTOR信号调节这种吸收,这表明circRNAs充当危险信号.
科学领域:
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 循环RNAs (circRNAs) 是稳定的,在无细胞环境中发现的共闭合的RNA分子.
- 它们在细胞外RNA混合物中的存在引发了关于它们的起源和生物作用的问题.
- 了解外源性circRNAs的细胞相互作用对于其潜在的治疗或病理影响至关重要.
研究的目的:
- 研究人类免疫细胞对外源性circRNAs的细胞吸收机制.
- 阐明circRNA内部化的细胞内命运和功能后果.
- 确定参与circRNA识别和吸收的关键分子调节者.
主要方法:
- 利用人类髓状细胞和B细胞模型进行吸收研究.
- 进行了circRNA内部化的动力分析 (能量依赖,和).
- 采用了基因组规模的CRISPR屏幕和化学抑制剂研究.
- 在circRNA吸收后,研究了抗原呈现和免疫激活.
主要成果:
- 人类髓状细胞和B细胞选择性地内化细胞外环RNAs.
- 巨细胞的吸收是快速的,能源依赖的,和可和的,涉及受体介导的细胞和巨细胞.
- 内部化的circRNAs可以被翻译并导致抗原呈现,根据内部化路径产生不同的免疫结果.
- 巨食肉受体1 (MSR1),Toll-like受体和mTOR信号被确定为关键调节者.
结论:
- 外源性circRNAs通过特定的,受调节的途径被免疫细胞识别和内化.
- 循环RNA的吸收可以触发天生的免疫反应,并通过抗原呈现影响适应性免疫力.
- 这些发现将无细胞circRNA定位为潜在的"吃我"信号和与危险相关的分子模式.
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