A deregulated immune response to gliadin causes a decreased villus height in DQ8 transgenic mice

Rossana D'Arienzo, Rosita Stefanile, Francesco Maurano, Diomira Luongo, Paolo Bergamo, Giuseppe Mazzarella, Riccardo Troncone, Salvatore Auricchio, Chella David, Mauro Rossi

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Celiac disease (CD) is an enteropathy triggered by gluten and mediated by CD4+T cells. A complete understanding of CD immunopathogenesis has been hindered due to the lack of adequate in vivo models. Here, we explored the effect of the inhibition of COX by indomethacin in wheat gliadin-sensitized transgenic mice expressing the HLA-DQ8 heterodimer, a molecule associated with CD. Treated mice showed a gliadin-specific immune response with a significant reduction of villus height, not linked to crypt hyperplasia and to expansion of intraepithelial T cells. Notably, treated mice showed increased numbers of CD25+ and apoptotic cells in the lamina propria, whereas high basal levels of IFN-γ secretion, along with a reduced gliadin-specific IL-2 expression were detected in MLN. Biochemical assessment of the lesion revealed increased mRNA of Lamb3 and Adamts2, encoding for ECM proteins, and enhanced activities of metalloproteinases MMP1, 2 and 7. We conclude that an intestinal sensitivity to gliadin, in connection with COX inhibition, caused a decreased villus height in DQ8 tg mice. The lesion was induced by a deregulated mucosal cell immunity to gliadin, thus triggering activation of a specific ECM protein pathway responsible for lamina propria remodeling.

Original languageEnglish (US)
Pages (from-to)3552-3561
Number of pages10
JournalEuropean Journal of Immunology
Volume39
Issue number12
DOIs
StatePublished - Dec 1 2009

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Keywords

  • Inflammation
  • Mucosa
  • T cells
  • Transgenic mice

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

D'Arienzo, R., Stefanile, R., Maurano, F., Luongo, D., Bergamo, P., Mazzarella, G., Troncone, R., Auricchio, S., David, C., & Rossi, M. (2009). A deregulated immune response to gliadin causes a decreased villus height in DQ8 transgenic mice. European Journal of Immunology, 39(12), 3552-3561. https://doi.org/10.1002/eji.200839161