The gut has a specific vascular barrier that controls trafficking of antigens and microbiota into the bloodstream. However, the molecular mechanisms regulating the maintenance of this vascular barrier remain elusive. Here, we identified Caspase-8 as a pro-survival factor in mature intestinal endothelial cells that is required to actively maintain vascular homeostasis in the small intestine in an organ-specific manner. In particular, we find that deletion of Caspase-8 in endothelial cells results in small intestinal hemorrhages and bowel inflammation, while all other organs remained unaffected. We also show that Caspase-8 seems to be particularly needed in lymphatic endothelial cells to maintain gut homeostasis. Our work demonstrates that endothelial cell dysfunction, leading to the breakdown of the gut-vascular barrier, is an active driver of chronic small intestinal inflammation, highlighting the role of the intestinal vasculature as a safeguard of organ function.

中文翻译：

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内皮细胞中的 Caspase-8 维持肠道稳态并预防小鼠小肠炎症

肠道有一个特殊的血管屏障，可以控制抗原和微生物群进入血液的运输。然而，调节这种血管屏障维持的分子机制仍然难以捉摸。在这里，我们将 Caspase-8 鉴定为成熟肠内皮细胞中的促生存因子，它需要以器官特异性方式积极维持小肠中的血管稳态。特别是，我们发现内皮细胞中 Caspase-8 的缺失会导致小肠出血和肠道炎症，而所有其他器官均不受影响。我们还表明，淋巴管内皮细胞似乎特别需要 Caspase-8 来维持肠道稳态。我们的工作表明，内皮细胞功能障碍会导致肠血管屏障的破坏，