干扰素诱导潜力的单细胞异质性是可遗传的,由细胞状态的变化决定
Elizabeth A Thayer1, Gabriela Shipman1, Joel Rivera-Cardona1
1Department of Microbiology, University of Illinois Urbana-Champaign, Urbana, IL, USA.
bioRxiv : the preprint server for biology
|December 19, 2025
概括
产生干扰子 (IFN) 的细胞差异源于它们的信号状态,而不是刺激感知. 这种先天免疫变异是遗传的,影响抗病毒防御.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 病毒学 病毒学
背景情况:
- I型和III型干扰素 (IFN) 对于抗病毒防御至关重要.
- IFN的产生通常仅限于一小部分受感染的细胞,从而产生异质性.
研究的目的:
- 调查干扰素诱导潜力的细胞异质性的来源.
- 确定调节干扰素生产变异性的分子机制.
主要方法:
- 采用了单细胞分析技术.
- 研究了强化细胞信号状态的作用,特别是c-Jun N-终端激酶 (JNK) 和激活蛋白 (AP) -1通路.
- 使用基于药物的信号通路抑制.
主要成果:
- 在IFN诱导中,细胞异质性是由性细胞信号的变化驱动的,而不是刺激感应.
- 基线JNK和AP-1信号水平与IFNL1表达的倾向相关.
- 抑制JNK信号消除了对免疫刺激性RNA的先天抗病毒反应.
- 这种IFN诱导潜力的异质性是可遗传的,并且在细胞代中稳定.
结论:
- 信号状态的内在细胞对细胞的变异性显著影响先天免疫反应.
- 了解这种异质性是理解干扰素诱导变异性及其对抗病毒免疫力的关键.
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