Department of Biomedical and Clinical Sciences (BKV), Linköping University, Linköping, Sweden.
Int Rev Cell Mol Biol. 2021;358:133-164. doi: 10.1016/bs.ircmb.2020.09.007. Epub 2020 Oct 28.
The intestinal epithelium limits host-luminal interactions and maintains gut homeostasis. Breakdown of the epithelial barrier and villous atrophy are hallmarks of coeliac disease. Besides the well characterized immune-mediated epithelial damage induced in coeliac mucosa, constitutional changes and early gluten direct effects disturb intestinal epithelial cells. The subsequent modifications in key epithelial signaling pathways leads to outnumbered immature epithelial cells that, in turn, facilitate epithelial dysfunction, promote crypt hyperplasia, and increase intestinal permeability. Consequently, underlying immune cells have a greater access to gluten, which boosts the proinflammatory immune response against gluten and positively feedback the epithelial damage loop. Gluten-free diet is an indispensable treatment for coeliac disease patients, but additional therapies are under development, including those that reinforce intestinal epithelial healing. In this chapter, we provide an overview of intestinal epithelial cell disturbances that develop during gluten intake in coeliac disease mucosa.
肠上皮限制了宿主-腔交互作用并维持肠道内稳态。肠上皮屏障的破坏和绒毛萎缩是乳糜泻的特征性标志。除了在乳糜泻黏膜中已被充分描述的免疫介导的上皮损伤外，固有改变和早期谷蛋白的直接作用会扰乱肠上皮细胞。随后关键上皮信号通路的改变导致未成熟的上皮细胞数量增加，而这反过来又会导致上皮功能障碍、促进隐窝增生，并增加肠道通透性。因此，潜在的免疫细胞更容易接触到麸质，从而增强了针对麸质的促炎免疫反应，并对上皮损伤循环产生正反馈。无麸质饮食是乳糜泻患者不可或缺的治疗方法，但正在开发其他治疗方法，包括那些能加强肠上皮愈合的方法。在本章中，我们概述了在乳糜泻黏膜中摄入麸质时发生的肠上皮细胞紊乱。
