Araya, R. E., Gomez Castro, M. F., Carasi, P., McCarville, J. L., Jury, J., Mowat, A. M., Verdu, E. F. and Chirdo, F. G. (2016) Mechanisms of innate immune activation by gluten peptide p31-43 in mice. American Journal of Physiology: Gastrointestinal and Liver Physiology, 311(1), G40-G49. (doi: 10.1152/ajpgi.00435.2015) (PMID:27151946)
|
Text
155549.pdf - Accepted Version 13MB |
Abstract
Celiac disease (CD) is an immune-mediated enteropathy triggered by gluten in genetically susceptible individuals. Innate immunity contributes to the pathogenesis of CD, but the mechanisms remain poorly understood. Although previous in vitro work suggests that gliadin peptide p31-43 acts as an innate immune trigger, the underlying pathways are unclear and have not been explored in vivo. Here we show that intraluminal delivery of p31-43 induces morphological changes in the small intestinal mucosa of normal mice consistent with those seen in CD, including increased cell death and expression of inflammatory mediators. The effects of p31-43 were dependent on MyD88 and type I IFNs, but not Toll-like receptor 4 (TLR4), and were enhanced by coadministration of the TLR3 agonist polyinosinic:polycytidylic acid. Together, these results indicate that gliadin peptide p31-43 activates the innate immune pathways in vivo, such as IFN-dependent inflammation, relevant to CD. Our findings also suggest a common mechanism for the potential interaction between dietary gluten and viral infections in the pathogenesis of CD.
Item Type: | Articles |
---|---|
Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Mowat, Professor Allan |
Authors: | Araya, R. E., Gomez Castro, M. F., Carasi, P., McCarville, J. L., Jury, J., Mowat, A. M., Verdu, E. F., and Chirdo, F. G. |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
Journal Name: | American Journal of Physiology: Gastrointestinal and Liver Physiology |
Publisher: | American Physiological Society |
ISSN: | 0193-1857 |
ISSN (Online): | 1522-1547 |
Published Online: | 05 May 2016 |
Copyright Holders: | Copyright © 2016 American Physiological Society |
First Published: | First published in American Journal of Physiology: Gastrointestinal and Liver Physiology 311(1): G40-49 |
Publisher Policy: | Reproduced in accordance with the publisher copyright policy |
University Staff: Request a correction | Enlighten Editors: Update this record