Celiac.com 11/21/2011 - Celiac disease is common in people with type 1 diabetes (T1D). These people can show Abs reactions against tissue transglutaminase, the prime trigger in celiac disease. In short, gliadin seems to play a role in type 1 diabetes pathogenesis.
An international research team set out to investigate whether gliadin contributes to enteropathy and insulitis in NOD-DQ8 mice, an animal model that does not spontaneously develop T1D.
Researchers know that gliadin-sensitized NOD-DQ8 mice develop moderate enteropathy, intraepithelial lymphocytosis, and barrier dysfunction, but do not develop insulitis. The team administered anti-CD25 mAbs before gliadin-sensitization induced partial depletion of CD25+Foxp3+ T cells, which triggered severe insulitis, but did not worsen mucosal dysfunction.
The team isolated CD4+ T cells isolated from pancreatic lymph nodes. Those from mice that developed insulitis showed higher proliferation and pro-inflammatory cytokines after incubation with gliadin, but not with BSA. CD4+ T cells isolated from non-sensitized control mice showed no response to gliadin or BSA.
From these observations, the team concluded that gliadin sensitization triggered moderate enteropathy in NOD-DQ8 mice. However, triggering insulitis required gliadin-sensitization and partial systemic depletion of CD25+Foxp3+ T cells.
This study offers a model for explaining how mucosal intolerance to a dietary protein can trigger insulitis as a result of partial regulatory T cell deficiency.