在小鼠中NAIP/NLRC4炎症酶的动态由NAIP连接物度和上皮细胞分化调节

在小鼠中NAIP/NLRC4炎症酶的动态由NAIP连接物度和上皮细胞分化调节

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Updated: Sep 10, 2025

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Patrick Rosendahl Andreassen¹, Chantal Ernst², Marisa Pimentel Mendes²

¹Institute of Microbiology, Department of Biology, ETH Zurich, Zurich, Switzerland; Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.

Cell reports

|August 21, 2025

概括

肠道细胞中的NAIP/NLRC4炎症体显示出不同的反应,包括 pyroptosis,这取决于NAIP联体剂量和ASC聚合. 这种天生的免疫路径在上皮细胞中得到了微调.

科学领域:

免疫学
细胞生物学
胃肠病学

背景情况:

炎症酶对先天免疫至关重要, 检测危险信号并启动炎症反应,
对炎症酶激活的细胞类型特异性反应,特别是肠上皮细胞的反应,尚不完全理解.

研究的目的:

研究小鼠肠上皮细胞中NAIP/NLRC4炎症组的单细胞动态.
阐明NAIP对炎酶激活,ASC聚合和细胞命运的剂量依赖性影响.

主要方法:

使用含有 CARD (ASC)::GFP 报告系统的与亡相关的斑状蛋白质.
使用流体力显微镜来精确地将NAIP连接物输入单细胞.
使用光共振能量转移 (FRET) 报告器监测互白蛋白成熟和卡斯巴-1活性.

主要成果:

观察到与ASC聚合或不聚合发生的热,表明复杂的炎症酶激活途径.
对NAIP配体呈现剂量依赖的反应:高剂量诱导ASC聚合,而较低剂量导致细胞存活或ASC独立的细胞死亡.
通过细胞分化状态和NAIP连接剂剂量来影响酶-1动态和互白素成熟.

结论:

肠上皮细胞中的NAIP/NLRC4炎症酶反应高度调节,并且取决于环境.
炎症酶激活及其下游效应由配体度和细胞分化状态调节.
这项研究为肠道上皮的天生的免疫控制提供了新的见解.

关键词:

美国安全委员会 CP:免疫学干细胞研究流体FM 卡斯帕斯-1 类动物炎症组天生的免疫力肠道有机物病原体一个单元

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