Schumann Michael, Siegmund Britta, Schulzke Jörg D, Fromm Michael
Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Berlin, Germany; Berlin Institute of Health, Berlin, Germany; Berlin-Brandenburg School for Regenerative Therapies, Berlin, Germany.
Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Cell Mol Gastroenterol Hepatol. 2017 Jan 14;3(2):150-162. doi: 10.1016/j.jcmgh.2016.12.006. eCollection 2017 Mar.
In celiac disease (CD) a T-cell-mediated response to gluten is mounted in genetically predisposed individuals, resulting in a malabsorptive enteropathy histologically highlighted by villous atrophy and crypt hyperplasia. Recent data point to the epithelial layer as an under-rated hot spot in celiac pathophysiology to date. This overview summarizes current functional and genetic evidence on the role of the epithelial barrier in CD, consisting of the cell membranes and the apical junctional complex comprising sealing as well as ion and water channel-forming tight junction proteins and the adherens junction. Moreover, the underlying mechanisms are discussed, including apoptosis of intestinal epithelial cells, biology of intestinal stem cells, alterations in the apical junctional complex, transcytotic uptake of gluten peptides, and possible implications of a defective epithelial polarity. Current research is directed toward new treatment options for CD that are alternatives or complementary therapeutics to a gluten-free diet. Thus, strategies to target an altered epithelial barrier therapeutically also are discussed.
在乳糜泻（CD）中，遗传易感性个体对麸质产生T细胞介导的反应，导致吸收不良性肠病，其组织学特征为绒毛萎缩和隐窝增生。目前的数据表明，上皮层是迄今为止在乳糜泻病理生理学中被低估的热点。本综述总结了目前关于上皮屏障在CD中作用的功能和遗传学证据，上皮屏障由细胞膜和顶端连接复合体组成，顶端连接复合体包括封闭蛋白以及形成离子和水通道的紧密连接蛋白和黏着连接。此外，还讨论了潜在机制，包括肠上皮细胞凋亡、肠干细胞生物学、顶端连接复合体的改变、麸质肽的转胞吞摄取以及上皮极性缺陷的可能影响。当前的研究致力于寻找针对CD的新治疗选择，这些治疗方法是无麸质饮食的替代或补充疗法。因此，还讨论了针对改变的上皮屏障进行治疗的策略。
