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

Autores
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.
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Galipeau, Heather J.. McMaster University Medical Centre; Canadá
Fil: Rulli, Nestor Ezequiel. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Jury, Jennifer. McMaster University Medical Centre; Canadá
Fil: Huang, Xianxi. McMaster University Medical Centre; Canadá
Fil: Araya, Romina Elizabeth. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Murray, Joseph A.. Mayo Clinic Cancer Center; Estados Unidos
Fil: David, Chella S.. Mayo Clinic Cancer Center; Estados Unidos
Fil: Chirdo, Fernando Gabriel. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: McCoy, Kathy D.. McMaster University Medical Centre; Canadá
Fil: Verdu, Elena F.. McMaster University Medical Centre; Canadá
Materia
INTESTINE
DIABETES
INNATE IMMUNITY
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/105196

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network_name_str CONICET Digital (CONICET)
spelling Sensitization to gliadin induces moderate enteropathy and insulitis in nonobese Diabetic-DQ8 miceGalipeau, Heather J.Rulli, Nestor EzequielJury, JenniferHuang, XianxiAraya, Romina ElizabethMurray, Joseph A.David, Chella S.Chirdo, Fernando GabrielMcCoy, Kathy D.Verdu, Elena F.INTESTINEDIABETESINNATE IMMUNITYhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Celiac 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.Fil: Galipeau, Heather J.. McMaster University Medical Centre; CanadáFil: Rulli, Nestor Ezequiel. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Jury, Jennifer. McMaster University Medical Centre; CanadáFil: Huang, Xianxi. McMaster University Medical Centre; CanadáFil: Araya, Romina Elizabeth. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Murray, Joseph A.. Mayo Clinic Cancer Center; Estados UnidosFil: David, Chella S.. Mayo Clinic Cancer Center; Estados UnidosFil: Chirdo, Fernando Gabriel. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: McCoy, Kathy D.. McMaster University Medical Centre; CanadáFil: Verdu, Elena F.. McMaster University Medical Centre; CanadáAmerican Association of Immunologists2011-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/105196Galipeau, 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; 4338-43460022-1767CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.4049/jimmunol.1100854info:eu-repo/semantics/altIdentifier/url/https://www.jimmunol.org/content/187/8/4338info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:51:15Zoai:ri.conicet.gov.ar:11336/105196instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:51:15.301CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Sensitization to gliadin induces moderate enteropathy and insulitis in nonobese Diabetic-DQ8 mice
title Sensitization to gliadin induces moderate enteropathy and insulitis in nonobese Diabetic-DQ8 mice
spellingShingle Sensitization to gliadin induces moderate enteropathy and insulitis in nonobese Diabetic-DQ8 mice
Galipeau, Heather J.
INTESTINE
DIABETES
INNATE IMMUNITY
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
dc.creator.none.fl_str_mv 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.
author Galipeau, Heather J.
author_facet 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.
author_role author
author2 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.
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv INTESTINE
DIABETES
INNATE IMMUNITY
topic INTESTINE
DIABETES
INNATE IMMUNITY
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv 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.
Fil: Galipeau, Heather J.. McMaster University Medical Centre; Canadá
Fil: Rulli, Nestor Ezequiel. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Jury, Jennifer. McMaster University Medical Centre; Canadá
Fil: Huang, Xianxi. McMaster University Medical Centre; Canadá
Fil: Araya, Romina Elizabeth. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Murray, Joseph A.. Mayo Clinic Cancer Center; Estados Unidos
Fil: David, Chella S.. Mayo Clinic Cancer Center; Estados Unidos
Fil: Chirdo, Fernando Gabriel. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: McCoy, Kathy D.. McMaster University Medical Centre; Canadá
Fil: Verdu, Elena F.. McMaster University Medical Centre; Canadá
description 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.
publishDate 2011
dc.date.none.fl_str_mv 2011-10
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/105196
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
url http://hdl.handle.net/11336/105196
identifier_str_mv 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
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.4049/jimmunol.1100854
info:eu-repo/semantics/altIdentifier/url/https://www.jimmunol.org/content/187/8/4338
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Association of Immunologists
publisher.none.fl_str_mv American Association of Immunologists
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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