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Open AccessArticle

Celiac Disease Monocytes Induce a Barrier Defect in Intestinal Epithelial Cells

Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Charité – Universitätsmedizin Berlin, 12203 Berlin, Germany
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(22), 5597; (registering DOI)
Received: 16 October 2019 / Revised: 5 November 2019 / Accepted: 5 November 2019 / Published: 9 November 2019
(This article belongs to the Special Issue The Tight Junction and Its Proteins: More Than Just a Barrier)
Intestinal epithelial barrier function in celiac disease (CeD) patients is altered. However, the mechanism underlying this effect is not fully understood. The aim of the current study was to evaluate the role of monocytes in eliciting the epithelial barrier defect in CeD. For this purpose, human monocytes were isolated from peripheral blood mononuclear cells (PBMCs) from active and inactive CeD patients and healthy controls. PBMCs were sorted for expression of CD14 and co-cultured with intestinal epithelial cells (IECs, Caco2BBe). Barrier function, as well as tight junctional alterations, were determined. Monocytes were characterized by profiling of cytokines and surface marker expression. Transepithelial resistance was found to be decreased only in IECs that had been exposed to celiac monocytes. In line with this, tight junctional alterations were found by confocal laser scanning microscopy and Western blotting of ZO-1, occludin, and claudin-5. Analysis of cytokine concentrations in monocyte supernatants revealed higher expression of interleukin-6 and MCP-1 in celiac monocytes. However, surface marker expression, as analyzed by FACS analysis after immunostaining, did not reveal significant alterations in celiac monocytes. In conclusion, CeD peripheral monocytes reveal an intrinsically elevated pro-inflammatory cytokine pattern that is associated with the potential of peripheral monocytes to affect barrier function by altering TJ composition. View Full-Text
Keywords: barrier function; tight junction assembly; monocytes; celiac disease barrier function; tight junction assembly; monocytes; celiac disease
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Delbue, D.; Cardoso-Silva, D.; Branchi, F.; Itzlinger, A.; Letizia, M.; Siegmund, B.; Schumann, M. Celiac Disease Monocytes Induce a Barrier Defect in Intestinal Epithelial Cells. Int. J. Mol. Sci. 2019, 20, 5597.

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