Defective tight junctions in refractory celiac disease.
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.
Department of Gastroenterology, Infectious Diseases and Rheumatology, Berlin, Germany. michael.schumann@charite.de
Michael
M
Schumann
Sarah
S
Kamel
Marie-Luise
ML
Pahlitzsch
Lydia
L
Lebenheim
Claudia
C
May
Michael
M
Krauss
Michael
M
Hummel
Severin
S
Daum
Michael
M
Fromm
Jörg-Dieter
JD
Schulzke
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D018938:Caco-2 Cells; D016022:Case-Control Studies; D002446:Celiac Disease / Q000276:immunology / Q000503:physiopathology*; D057167:Claudins / Q000378:metabolism; D058266:Dielectric Spectroscopy; D004705:Endocytosis; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000503:physiopathology; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013347:Subcellular Fractions / Q000378:metabolism; D019108:Tight Junctions / Q000502:physiology*
D057167:Claudins; D011948:Receptors, Antigen, T-Cell