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

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 in...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Galipeau, Heather J., Rulli, Néstor E., Jury, Jennifer, Huang, Xianxi, Araya, Romina Elizabeth, Murray, Joseph A., David, Chella S., Chirdo, Fernando Gabriel, McCoy, Kathy D., Verdu, Elena F.
Formato: Articulo
Lenguaje:Inglés
Publicado: 2011
Materias:
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/83686
Aporte de:
id I19-R120-10915-83686
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Exactas
Ciencias Médicas
diabetes
gliadin sensitization
moderate enteropathy
spellingShingle Ciencias Exactas
Ciencias Médicas
diabetes
gliadin sensitization
moderate enteropathy
Galipeau, Heather J.
Rulli, Néstor E.
Jury, Jennifer
Huang, Xianxi
Araya, Romina Elizabeth
Murray, Joseph A.
David, Chella S.
Chirdo, Fernando Gabriel
McCoy, Kathy D.
Verdu, Elena F.
Sensitization to gliadin induces moderate enteropathy and insulitis in nonobese diabetic-DQ8 mice
topic_facet Ciencias Exactas
Ciencias Médicas
diabetes
gliadin sensitization
moderate enteropathy
description 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<SUP>+</SUP>Foxp3<SUP>+</SUP> T cells and led to severe insulitis, but did not exacerbate mucosal dysfunction. CD4<SUP>+</SUP>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<SUP>+</SUP> 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<SUP>+</SUP>Foxp3<SUP>+</SUP> 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.
format Articulo
Articulo
author Galipeau, Heather J.
Rulli, Néstor E.
Jury, Jennifer
Huang, Xianxi
Araya, Romina Elizabeth
Murray, Joseph A.
David, Chella S.
Chirdo, Fernando Gabriel
McCoy, Kathy D.
Verdu, Elena F.
author_facet Galipeau, Heather J.
Rulli, Néstor E.
Jury, Jennifer
Huang, Xianxi
Araya, Romina Elizabeth
Murray, Joseph A.
David, Chella S.
Chirdo, Fernando Gabriel
McCoy, Kathy D.
Verdu, Elena F.
author_sort Galipeau, Heather J.
title Sensitization to gliadin induces moderate enteropathy and insulitis in nonobese diabetic-DQ8 mice
title_short Sensitization to gliadin induces moderate enteropathy and insulitis in nonobese diabetic-DQ8 mice
title_full Sensitization to gliadin induces moderate enteropathy and insulitis in nonobese diabetic-DQ8 mice
title_fullStr Sensitization to gliadin induces moderate enteropathy and insulitis in nonobese diabetic-DQ8 mice
title_full_unstemmed Sensitization to gliadin induces moderate enteropathy and insulitis in nonobese diabetic-DQ8 mice
title_sort sensitization to gliadin induces moderate enteropathy and insulitis in nonobese diabetic-dq8 mice
publishDate 2011
url http://sedici.unlp.edu.ar/handle/10915/83686
work_keys_str_mv AT galipeauheatherj sensitizationtogliadininducesmoderateenteropathyandinsulitisinnonobesediabeticdq8mice
AT rullinestore sensitizationtogliadininducesmoderateenteropathyandinsulitisinnonobesediabeticdq8mice
AT juryjennifer sensitizationtogliadininducesmoderateenteropathyandinsulitisinnonobesediabeticdq8mice
AT huangxianxi sensitizationtogliadininducesmoderateenteropathyandinsulitisinnonobesediabeticdq8mice
AT arayarominaelizabeth sensitizationtogliadininducesmoderateenteropathyandinsulitisinnonobesediabeticdq8mice
AT murrayjosepha sensitizationtogliadininducesmoderateenteropathyandinsulitisinnonobesediabeticdq8mice
AT davidchellas sensitizationtogliadininducesmoderateenteropathyandinsulitisinnonobesediabeticdq8mice
AT chirdofernandogabriel sensitizationtogliadininducesmoderateenteropathyandinsulitisinnonobesediabeticdq8mice
AT mccoykathyd sensitizationtogliadininducesmoderateenteropathyandinsulitisinnonobesediabeticdq8mice
AT verduelenaf sensitizationtogliadininducesmoderateenteropathyandinsulitisinnonobesediabeticdq8mice
bdutipo_str Repositorios
_version_ 1764820488894283778