粘膜胰岛素受体的激活会通过通过EZH2促进组织内存T细胞分化而加剧肠道炎症

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Updated: Jul 5, 2025

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Induced Differentiation of M Cell-like Cells in Human Stem Cell-derived Ileal Enteroid Monolayers

Published on: July 26, 2019

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Teming Li^1,2, Ben Han¹, Liucan Wang¹

¹Department of General Surgery, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China.

Journal of translational medicine

|January 19, 2024

概括

在肠道中准胰岛素受体和EZH2可能治疗炎症性肠病 (IBD). 抑制EZH2通过调节组织内存T细胞 (TRM) 分化来缓解IBD.

科学领域:

免疫学免疫学免疫学
胃肠病学胃肠病学
分子生物学分子生物学

背景情况:

炎症性肠病 (IBD) 是一种带有肠道免疫异常的自身免疫性疾病,导致全球显著的发病率.
目前用于IBD的治疗药物提供的益处有限,需要探索新的治疗点.
组织内存T细胞 (TRM) 在IBD等自身免疫性疾病中发挥着核心作用,但它们的分化机制需要进一步研究.

研究的目的:

在慢性结肠炎模型中研究胰岛素途径在肠道TRM分化中的作用.
为了确定参与TRM分化中的胰岛素途径的下游目标.
评估针对胰岛素途径及其下游效应因子用于IBD治疗的治疗潜力.

主要方法:

在硫酸 (DSS) 诱导的慢性结肠炎中分析了肠内皮质淋巴细胞 (IEL) 的mRNA和lncRNA概况.
研究了直肠胰岛素灌注对结肠炎和IELs的影响.
利用EZH2条件淘汰赛小鼠 (EZH2^fl/flCD4^cre) 来研究EZH2在TRM分化和结肠炎中的作用.

主要成果:

直肠胰岛素灌注加剧了结肠炎,破坏了IEL亚组,并增加了TNF-ɑ和IL-17的表达.
在大肠炎中,胰岛素受体 (INSR) 表达减少.
在EZH2^fl/flCD4^cre小鼠中,EZH2抑制和遗传删除缓解了结肠炎,减少了炎症标志物,并使IEL亚组正常化,表明抑制了TRM分化.

结论:

肠粘膜T细胞胰岛素受体信号传递通过EZH2.2促进肠道TRM分化.
针对结肠INSR和EZH2,通过调节TRM,为IBD提供了一个潜在的治疗策略.
在活性结肠炎期间建议使用胰岛素受体抑制剂,而不是胰岛素;EZH2抑制显示出治疗前景,但由于其在TRM分化中的作用,在抗瘤应用中存在局限性.

关键词:

炎症性肠病是一种炎症性肠病.胰岛素受体的胰岛素受体是什么肠道内皮细胞内淋巴细胞.组织内存T细胞组织内存T细胞

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