Defective tight junctions in refractory celiac disease
Article first published online: 25 JUN 2012
© 2012 New York Academy of Sciences.
Annals of the New York Academy of Sciences
Volume 1258, Barriers and Channels Formed by Tight Junction Proteins II pages 43–51, July 2012
How to Cite
Schumann, M., Kamel, S., Pahlitzsch, M.-L., Lebenheim, L., May, C., Krauss, M., Hummel, M., Daum, S., Fromm, M. and Schulzke, J.-D. (2012), Defective tight junctions in refractory celiac disease. Annals of the New York Academy of Sciences, 1258: 43–51. doi: 10.1111/j.1749-6632.2012.06565.x
- Issue published online: 25 JUN 2012
- Article first published online: 25 JUN 2012
- celiac disease;
- refractory celiac disease;
- epithelial barrier;
- tight junction
In celiac disease, the gut-associated immune system is activated in response to the ingestion of gluten, causing an atrophy of the small intestinal mucosa. Although this condition is, in most cases, responsive to a gluten-free diet, celiac disease refractory to treatment occurs in a small percentage of celiacs. An epithelial barrier defect is known to be an integral part of celiac pathophysiology. However, the mucosa in refractory celiac disease underlies a constant inflammatory process. The epithelial barrier has not been addressed in this condition so far. Herein, the tight junction-associated barrier in refractory celiac disease is investigated functionally and structurally. Although normally expressed in celiac disease, claudin-4 is shown to be downregulated in refractory cases, presumably by two mechanisms, reduced protein expression and increased claudin endocytosis. Furthermore, the tightening claudin-5 is downregulated and the pore-forming claudin-2 is upregulated.