遇见数据集

Dataset related to article "mTOR-Dependent Stimulation of IL20RA Orchestrates Immune Cell Trafficking through Lymphatic Endothelium in Patients with Crohn's Disease."

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Zenodo2020-08-01 更新2026-05-25 收录
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Crohn's disease (CD) is a chronic inflammatory condition that can affect different portions of the gastrointestinal tract. Lymphatic drainage was demonstrated to be dysfunctional in CD pathogenesis, ultimately causing the failure of the resolution of intestinal inflammation. To investigate the molecular mechanisms underlying these dysfunctions, we isolated human intestinal lymphatic endothelial cells (HILECs) from surgical specimens of patients undergoing resection for complicated CD (CD HILEC) and from a disease-free margin of surgical specimens of patients undergoing resection for cancer (healthy HILEC). Both cell types underwent transcriptomic profiling, and their barrier functionality was tested using a transwell-based co-culture system between HILEC and lamina propria mononuclear cells (LPMCs). Results showed CD HILEC displayed a peculiar transcriptomic signature that highlighted mTOR signaling as an orchestrator of leukocyte trafficking through the lymphatic barrier of CD patients. Moreover, we demonstrated that LPMC transmigration through the lymphatic endothelium of patients with CD depends on the capability of mTOR to trigger interleukin 20 receptor subunit α (IL20RA)-mediated intracellular signaling. Conclusively, our study suggests that leukocyte trafficking through the intestinal lymphatic microvasculature can be controlled by modulating IL20RA, thus leading to the resolution of chronic inflammation in patients with CD.

克罗恩病(Crohn's disease, CD)是一种可累及胃肠道不同节段的慢性炎症性疾病。已有研究证实,淋巴引流功能异常参与克罗恩病的发病过程,最终导致肠道炎症无法消退。为探究此类功能异常的分子机制,本研究从因复杂性克罗恩病接受切除术的患者手术标本中分离得到人体肠道淋巴内皮细胞(human intestinal lymphatic endothelial cells, HILECs),并从因癌症接受切除术的患者手术标本的无病切缘处分离得到健康人体肠道淋巴内皮细胞;对两种细胞均开展转录组学分析,并采用基于Transwell的共培养体系,将HILECs与固有层单核细胞(lamina propria mononuclear cells, LPMCs)共培养以检测其屏障功能。结果显示,CD来源HILECs具有独特的转录组特征,提示mTOR信号通路可作为克罗恩病患者淋巴屏障中白细胞转运的调控核心;此外,本研究证实,克罗恩病患者的固有层单核细胞跨淋巴内皮迁移的过程,依赖于mTOR触发白细胞介素20受体亚基α(interleukin 20 receptor subunit α, IL20RA)介导的细胞内信号通路。综上,本研究表明,通过调控IL20RA可干预肠道淋巴微脉管系统中的白细胞转运过程,进而实现克罗恩病患者慢性炎症的消退。

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Zenodo
创建时间:
2020-03-13
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