Sensitization to gliadin induces moderate enteropathy and insulitis in nonobese diabetic-DQ8 mice

Heather J. Galipeau, Nestor E. Rulli, Jennifer Jury, Xianxi Huang, Romina Araya, Joseph A. Murray, Chella S. David, Fernando G. Chirdo, Kathy D. McCoy, Elena F. Verdu

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Celiac disease (CD) is frequently diagnosed in patients with type 1 diabetes (T1D), and T1D patients can exhibit Abs against tissue transglutaminase, the auto-antigen in CD. Thus, gliadin, the trigger in CD, has been suggested to have a role in T1D pathogenesis. The objective of this study was to investigate whether gliadin contributes to enteropathy and insulitis in NOD-DQ8 mice, an animal model that does not spontaneously develop T1D. Gliadin-sensitized NOD-DQ8 mice developed moderate enteropathy, intraepithelial lymphocytosis, and barrier dysfunction, but not insulitis. Administration of anti-CD25 mAbs before gliadin-sensitization induced partial depletion of CD25+Foxp3+ T cells and led to severe insulitis, but did not exacerbate mucosal dysfunction. CD4+T cells isolated from pancreatic lymph nodes of mice that developed insulitis showed increased proliferation and proinflammatory cytokines after incubation with gliadin but not with BSA. CD4+ T cells isolated from nonsensitized controls did not response to gliadin or BSA. In conclusion, gliadin sensitization induced moderate enteropathy in NOD-DQ8 mice. However, insulitis development required gliadin-sensitization and partial systemic depletion of CD25 +Foxp3+ T cells. This humanized murine model provides a mechanistic link to explain how the mucosal intolerance to a dietary protein can lead to insulitis in the presence of partial regulatory T cell deficiency.

Original languageEnglish (US)
Pages (from-to)4338-4346
Number of pages9
JournalJournal of Immunology
Volume187
Issue number8
DOIs
StatePublished - Oct 15 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Galipeau, H. J., Rulli, N. E., Jury, J., Huang, X., Araya, R., Murray, J. A., David, C. S., Chirdo, F. G., McCoy, K. D., & Verdu, E. F. (2011). Sensitization to gliadin induces moderate enteropathy and insulitis in nonobese diabetic-DQ8 mice. Journal of Immunology, 187(8), 4338-4346. https://doi.org/10.4049/jimmunol.1100854