帕内特细胞SIRT1缺陷通过调节肠道微生物群来增加肠道抗压能力
Liz M Garcia-Peterson1,2, Alicia S Wellman1, Xiaojiang Xu3,4
1Molecular and Cellular Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, USA.
EMBO reports
|March 14, 2026
概括
科学家们发现,Paneth细胞 (肠道免疫细胞) 中的SIRT1通常会抑制它们的功能. 移除SIRT1可以改善肠道健康和抗炎能力,揭示SIRT1在肠道应激反应中的新作用.
科学领域:
- 胃肠病学 胃肠病学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 帕内特细胞对于肠道平衡,微生物群和屏障功能至关重要.
- 功能障碍的帕内斯细胞有助于肠道炎症.
- 压力诱导的帕内斯细胞失调的机制尚未完全理解.
研究的目的:
- 研究SIRT1在帕内斯细胞功能和应激反应中的作用.
- 阐明SIRT1调节帕内斯细胞的分子机制.
主要方法:
- 使用了缺少SIRT1的淘汰赛小鼠,特别是在Paneth细胞中.
- 分析了Wnt信号传递和内质网膜应激通路.
- 评估了帕内斯细胞的丰富性,抗菌素的产生,以及对大肠炎的耐药性.
- 通过枯竭和便移植研究了肠道微生物群的作用.
主要成果:
- 删除帕内斯细胞SIRT1激活了Wnt信号传递和ATF4/ER应激通路.
- 在年轻小鼠中,SIRT1缺乏导致帕内斯细胞丰富度增加和抗菌的产生.
- 患有帕内斯细胞SIRT1缺陷的老年小鼠对免疫细胞扩张的保护得到了改善.
- 帕内斯细胞SIRT1缺陷赋予了对化学诱导的结肠炎的耐药性,部分是由肠道微生物群相互作用介导的.
结论:
- SIRT1细胞自主抑制帕内特细胞功能,并使肠表皮对压力敏感.
- 帕内斯细胞SIRT1缺陷通过调节帕内斯细胞功能和与肠道微生物群相互作用来改善结肠炎.
- 这些发现揭示了帕内斯细胞SIRT1在调节肠上皮质应激敏感性的新作用.
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