info:eu-repo/semantics/article
Sensitization to gliadin induces moderate enteropathy and insulitis in nonobese Diabetic-DQ8 mice
Fecha
2011-10Registro en:
Galipeau, Heather J.; Rulli, Nestor Ezequiel; Jury, Jennifer; Huang, Xianxi; Araya, Romina Elizabeth; et al.; Sensitization to gliadin induces moderate enteropathy and insulitis in nonobese Diabetic-DQ8 mice; American Association of Immunologists; Journal of Immunology; 187; 8; 10-2011; 4338-4346
0022-1767
CONICET Digital
CONICET
Autor
Galipeau, Heather J.
Rulli, Nestor Ezequiel
Jury, Jennifer
Huang, Xianxi
Araya, Romina Elizabeth
Murray, Joseph A.
David, Chella S.
Chirdo, Fernando Gabriel
McCoy, Kathy D.
Verdu, Elena F.
Resumen
Celiac Disease (CD) is frequently diagnosed in patients with type 1 diabetes (T1D), and T1D patients can exhibit antibodies against tissue transglutaminase, the auto-antigen in CD. Thus, gliadin, the trigger in CD, has been suggested to play 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 mucosal dysfunction, but no insulitis. Administration of anti-CD25 mAbs before sensitization induced partial depletion of CD25+Foxp3+ T-cells and led to insulitis. Mice that developed insulitis had increased pro-inflammatory cytokines in the mesenteric (MLN) and pancreatic lymph nodes (PLN). CD4+ T-cells isolated from PLN of mice that developed insulitis showed increased proliferation and proinflammatory cytokines after incubations with gliadin but not, with bovine serum albumin (BSA). In control mice, CD4+ T-cells from PLN did not proliferate in response to gliadin. In conclusion, gliadin sensitization induced moderate enteropathy in NOD-DQ8 mice but insulitis development required gliadin-sensitization and partial systemic depletion of CD25+Foxp3+ T-cells. This animal model provides a mechanistic link through which the dietary antigen gliadin, which triggers CD, modulates the onset of insulitis in the presence of partial regulatory T cell deficiency. Both innate and adaptive immune mechanisms related to gluten intolerance can be investigated in NOD-DQ8 mice.