在肠道上皮细胞中CARD14信号诱导肠道炎症和肠道过渡延迟
Aigerim Aidarova1,2, Marieke Carels1,2, Mira Haegman1,2
1Center for Inflammation Research, Unit of Molecular Signal Transduction in Inflammation, VIB, Ghent, Belgium.
EMBO molecular medicine
|October 23, 2025
概括
在肠道上皮细胞 (IEC) 中获得功能的CARD14突变会导致小鼠轻度炎症和运动减少. 这表明牛皮相关的CARD14变体和肠道疾病之间存在联系,影响肠道健康和感染易感性.
科学领域:
- 胃肠病学 胃肠病学
- 免疫学 免疫学 免疫学
- 遗传学 是一个遗传学.
背景情况:
- CARD14是一种NF-κB信号传递媒介,主要以其在皮肤免疫力中的作用而闻名.
- 罕见的CARD14变种与皮肤疾病如牛皮和亚托邦性皮肤炎有关.
- 在肠上皮细胞 (IEC) 中的CARD14表达表明在肠功能中可能发挥作用,但仍未被探索.
研究的目的:
- 研究CARD14在肠道中的功能,特别是IEC中的功能.
- 为了确定与牛皮相关的CARD14功能增益突变在肠道中的影响.
- 探索CARD14变体与肠道炎症,运动性和感染易感性之间的联系.
主要方法:
- 产生的转基因小鼠表达人类CARD14(E138A) 功能增益突变,特别是在IEC (CARD14(E138A) IEC小鼠).
- 评估了肠道炎症,上皮质完整性和肠道神经元功能.
- 分析了肠道移动性,肠道微生物群组成,以及对肠道细菌感染的易感性.
- 进行IEC的转录组分析以确定分子变化.
主要成果:
- CARD14 ((E138A) IEC小鼠表现出轻微的肠道炎症,没有表皮损伤.
- 观察到肠道运动率显著降低和直肠脱落.
- 肠神经元的生存和功能没有受到影响.
- 帕内斯细胞减少了抗微生物的表达,发现了微生物失生症和对肠道感染的易感性增加.
- 转录组分析显示,IEC的基因表达发生了改变.
结论:
- 在IEC中获得功能的CARD14突变可以导致轻度肠道炎症和减少动力.
- 这些发现表明,与牛皮相关的CARD14变异可能会使个人易患肠道疾病.
- CARD14(E138A) IEC小鼠作为一种有价值的模型,用于研究肠道炎症和运动障碍的IEC内在机制.
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