Intracellular Localization of Microbial Transglutaminase and Its Influence on the Transport of Gliadin in Enterocytes

Objective: Celiac disease (CD) is a systemic inflammatory disorder, characterized by the destruction of duodenal epithelium. The CD8+ T cells involved are associated with cross presentation. Besides other factors, the rising prevalence of CD might be induced by microbial transglutaminase (mTG) an enzyme frequently used in food production that shares enzymatic and antigenic properties of tissue transglutaminase (TG2), the autoantigen in CD. We hypothesized that mTG and gliadin are transported into the endoplasmic reticulum (ER), indicating cross presentation of both antigens. Methods: Apical incubation of duodenal biopsies from CD and control patients was performed with mTG alone or with mTG and simultaneously with Frazer's Fraction. Evaluation was carried out by immunofluorescence and electron microscopy. Results: 6-9% of the intracellular mTG and gliadin were transported to the ER of enterocytes. RACE cells (rapid uptake of antigen into the cytosol of enterocytes) displayed an enhanced antigen uptake into a dilated ER. mTG strongly localized at the basolateral membrane and the lamina propria (LP). Conclusions: mTG and gliadin are transported to the ER of enterocytes and to a greater extent to the ER of RACE cells, suggesting cross presentation of exogenous antigens. The strong localization of mTG at the basolateral membrane and the LP may also indicate a potential antigenic interaction with cells of the immune system. Since mTG may not only been taken up with food stuffs but could also be released by bacteria within the intestinal microbiota, further investigations are needed regarding the role of mTG in CD pathogenesis. Address correspondence and reprint requests to Klaus-Peter Zimmer, Department of Paediatrics, Justus-Liebig-University Giessen, Feulgenstraße 12, 35392 Giessen, Germany (e-mail: Klaus-Peter.Zimmer@paediat.med.uni-giessen.de);SebastianStricker,JustusLiebigUniversityGiessen,Giessen,Germany(e-mail:Sebastian.Stricker@paediat.med.uni-giessen.de). Received 27 April, 2018 Accepted 27 September, 2018 Conflicts of Interest and Source of Funding: No conflicts of interest declared. No external funding obtained. Intracellular localization of microbial transglutaminase and its influence on the transport of gliadin in enterocytes Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (www.jpgn.org). © 2018 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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