Gluten-Dependent Activation of CD4+ T Cells by MHC Class II–Expressing Epithelium
- Autores
- Rahmani, Sara; Galipeau, Heather J.; Clarizio, Alexandra V.; Wang, Xuanyu; Hann, Amber; Rueda, Gaston H.; Kirtikar, Utkarshini N.; Constante, Marco; Wulczynski, Mark; Su, Hsuan-Ming; Burchett, Rebecca; Bramson, Jonathan L.; Pinto Sanchez, Maria Ines; Stefanolo, Juan Pablo; Niveloni, Sonia; Surette, Michael G.; Murray, Joseph A.; Anderson, Robert P.; Bercik, Premysl; Caminero, Alberto; Chirdo, Fernando Gabriel; F. Didar, Tohid; Verdu, Elena F.
- Año de publicación
- 2024
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Background & Aims Intestinal epithelial cell (IEC) damage is a hallmark of celiac disease (CeD); however, its role in gluten-dependent T-cell activation is unknown. We investigated IEC-gluten-T-cell interactions in organoid monolayers expressing human major histocompatibility complex class II (HLA-DQ2.5), which facilitates gluten antigen recognition by CD4+ T cells in CeD. Methods Epithelial major histocompatibility complex class II (MHCII) was determined in active and treated CeD, and in nonimmunized and gluten-immunized DR3-DQ2.5 transgenic mice, lacking mouse MHCII molecules. Organoid monolayers from DR3-DQ2.5 mice were treated with or without interferon (IFN)-γ, and MHCII expression was evaluated by flow cytometry. Organoid monolayers and CD4+ T-cell co-cultures were incubated with gluten, predigested, or not by elastase-producing Pseudomonas aeruginosa or its lasB mutant. T-cell function was assessed based on proliferation, expression of activation markers, and cytokine release in the co-culture supernatants. Results Patients with active CeD and gluten-immunized DR3-DQ2.5 mice demonstrated epithelial MHCII expression. Organoid monolayers derived from gluten-immunized DR3-DQ2.5 mice expressed MHCII, which was upregulated by IFN-γ. In organoid monolayer T-cell co-cultures, gluten increased the proliferation of CD4+ T cells, expression of T-cell activation markers, and the release of interleukin-2, IFN-γ, and interleukin-15 in co-culture supernatants. Gluten metabolized by P aeruginosa, but not the lasB mutant, enhanced CD4+ T-cell proliferation and activation. Conclusions Gluten antigens are efficiently presented by MHCII-expressing IECs, resulting in the activation of gluten-specific CD4+ T cells, which is enhanced by gluten predigestion with microbial elastase. Therapeutics directed at IECs may offer a novel approach for modulating both adaptive and innate immunity in patients with CeD.
Fil: Rahmani, Sara. Mc Master University; Canadá
Fil: Galipeau, Heather J.. Mc Master University; Canadá
Fil: Clarizio, Alexandra V.. Mc Master University; Canadá
Fil: Wang, Xuanyu. Mc Master University; Canadá
Fil: Hann, Amber. Mc Master University; Canadá
Fil: Rueda, Gaston H.. Mc Master University; Canadá
Fil: Kirtikar, Utkarshini N.. Mc Master University; Canadá
Fil: Constante, Marco. Mc Master University; Canadá
Fil: Wulczynski, Mark. Mc Master University; Canadá
Fil: Su, Hsuan-Ming. Mc Master University; Canadá
Fil: Burchett, Rebecca. Mc Master University; Canadá
Fil: Bramson, Jonathan L.. Mc Master University; Canadá
Fil: Pinto Sanchez, Maria Ines. Mc Master University; Canadá
Fil: Stefanolo, Juan Pablo. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina
Fil: Niveloni, Sonia. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina
Fil: Surette, Michael G.. Mc Master University; Canadá
Fil: Murray, Joseph A.. Division Of Gastroenterology And Hepatology, Department; Estados Unidos
Fil: Anderson, Robert P.. Mackay Base Hospital, Mackay, Queensland, Australia;; Australia
Fil: Bercik, Premysl. Mc Master University; Canadá
Fil: Caminero, Alberto. Mc Master University; Canadá
Fil: Chirdo, Fernando Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina
Fil: F. Didar, Tohid. Mc Master University; Canadá
Fil: Verdu, Elena F.. Mc Master University; Canadá - Materia
-
celiac disease
organoid monolayer
MHC class II
T cell activation - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/266808
Ver los metadatos del registro completo
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Gluten-Dependent Activation of CD4+ T Cells by MHC Class II–Expressing EpitheliumRahmani, SaraGalipeau, Heather J.Clarizio, Alexandra V.Wang, XuanyuHann, AmberRueda, Gaston H.Kirtikar, Utkarshini N.Constante, MarcoWulczynski, MarkSu, Hsuan-MingBurchett, RebeccaBramson, Jonathan L.Pinto Sanchez, Maria InesStefanolo, Juan PabloNiveloni, SoniaSurette, Michael G.Murray, Joseph A.Anderson, Robert P.Bercik, PremyslCaminero, AlbertoChirdo, Fernando GabrielF. Didar, TohidVerdu, Elena F.celiac diseaseorganoid monolayerMHC class IIT cell activationhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Background & Aims Intestinal epithelial cell (IEC) damage is a hallmark of celiac disease (CeD); however, its role in gluten-dependent T-cell activation is unknown. We investigated IEC-gluten-T-cell interactions in organoid monolayers expressing human major histocompatibility complex class II (HLA-DQ2.5), which facilitates gluten antigen recognition by CD4+ T cells in CeD. Methods Epithelial major histocompatibility complex class II (MHCII) was determined in active and treated CeD, and in nonimmunized and gluten-immunized DR3-DQ2.5 transgenic mice, lacking mouse MHCII molecules. Organoid monolayers from DR3-DQ2.5 mice were treated with or without interferon (IFN)-γ, and MHCII expression was evaluated by flow cytometry. Organoid monolayers and CD4+ T-cell co-cultures were incubated with gluten, predigested, or not by elastase-producing Pseudomonas aeruginosa or its lasB mutant. T-cell function was assessed based on proliferation, expression of activation markers, and cytokine release in the co-culture supernatants. Results Patients with active CeD and gluten-immunized DR3-DQ2.5 mice demonstrated epithelial MHCII expression. Organoid monolayers derived from gluten-immunized DR3-DQ2.5 mice expressed MHCII, which was upregulated by IFN-γ. In organoid monolayer T-cell co-cultures, gluten increased the proliferation of CD4+ T cells, expression of T-cell activation markers, and the release of interleukin-2, IFN-γ, and interleukin-15 in co-culture supernatants. Gluten metabolized by P aeruginosa, but not the lasB mutant, enhanced CD4+ T-cell proliferation and activation. Conclusions Gluten antigens are efficiently presented by MHCII-expressing IECs, resulting in the activation of gluten-specific CD4+ T cells, which is enhanced by gluten predigestion with microbial elastase. Therapeutics directed at IECs may offer a novel approach for modulating both adaptive and innate immunity in patients with CeD.Fil: Rahmani, Sara. Mc Master University; CanadáFil: Galipeau, Heather J.. Mc Master University; CanadáFil: Clarizio, Alexandra V.. Mc Master University; CanadáFil: Wang, Xuanyu. Mc Master University; CanadáFil: Hann, Amber. Mc Master University; CanadáFil: Rueda, Gaston H.. Mc Master University; CanadáFil: Kirtikar, Utkarshini N.. Mc Master University; CanadáFil: Constante, Marco. Mc Master University; CanadáFil: Wulczynski, Mark. Mc Master University; CanadáFil: Su, Hsuan-Ming. Mc Master University; CanadáFil: Burchett, Rebecca. Mc Master University; CanadáFil: Bramson, Jonathan L.. Mc Master University; CanadáFil: Pinto Sanchez, Maria Ines. Mc Master University; CanadáFil: Stefanolo, Juan Pablo. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Niveloni, Sonia. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Surette, Michael G.. Mc Master University; CanadáFil: Murray, Joseph A.. Division Of Gastroenterology And Hepatology, Department; Estados UnidosFil: Anderson, Robert P.. Mackay Base Hospital, Mackay, Queensland, Australia;; AustraliaFil: Bercik, Premysl. Mc Master University; CanadáFil: Caminero, Alberto. Mc Master University; CanadáFil: Chirdo, Fernando Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: F. Didar, Tohid. Mc Master University; CanadáFil: Verdu, Elena F.. Mc Master University; CanadáW B Saunders Co-Elsevier Inc2024-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/266808Rahmani, Sara; Galipeau, Heather J.; Clarizio, Alexandra V.; Wang, Xuanyu; Hann, Amber; et al.; Gluten-Dependent Activation of CD4+ T Cells by MHC Class II–Expressing Epithelium; W B Saunders Co-Elsevier Inc; Gastroenterology; 167; 6; 8-2024; 1113-11280016-5085CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0016508524052119info:eu-repo/semantics/altIdentifier/doi/10.1053/j.gastro.2024.07.008info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:57:24Zoai:ri.conicet.gov.ar:11336/266808instacron: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:34982025-10-15 14:57:25.108CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Gluten-Dependent Activation of CD4+ T Cells by MHC Class II–Expressing Epithelium |
| title |
Gluten-Dependent Activation of CD4+ T Cells by MHC Class II–Expressing Epithelium |
| spellingShingle |
Gluten-Dependent Activation of CD4+ T Cells by MHC Class II–Expressing Epithelium Rahmani, Sara celiac disease organoid monolayer MHC class II T cell activation |
| title_short |
Gluten-Dependent Activation of CD4+ T Cells by MHC Class II–Expressing Epithelium |
| title_full |
Gluten-Dependent Activation of CD4+ T Cells by MHC Class II–Expressing Epithelium |
| title_fullStr |
Gluten-Dependent Activation of CD4+ T Cells by MHC Class II–Expressing Epithelium |
| title_full_unstemmed |
Gluten-Dependent Activation of CD4+ T Cells by MHC Class II–Expressing Epithelium |
| title_sort |
Gluten-Dependent Activation of CD4+ T Cells by MHC Class II–Expressing Epithelium |
| dc.creator.none.fl_str_mv |
Rahmani, Sara Galipeau, Heather J. Clarizio, Alexandra V. Wang, Xuanyu Hann, Amber Rueda, Gaston H. Kirtikar, Utkarshini N. Constante, Marco Wulczynski, Mark Su, Hsuan-Ming Burchett, Rebecca Bramson, Jonathan L. Pinto Sanchez, Maria Ines Stefanolo, Juan Pablo Niveloni, Sonia Surette, Michael G. Murray, Joseph A. Anderson, Robert P. Bercik, Premysl Caminero, Alberto Chirdo, Fernando Gabriel F. Didar, Tohid Verdu, Elena F. |
| author |
Rahmani, Sara |
| author_facet |
Rahmani, Sara Galipeau, Heather J. Clarizio, Alexandra V. Wang, Xuanyu Hann, Amber Rueda, Gaston H. Kirtikar, Utkarshini N. Constante, Marco Wulczynski, Mark Su, Hsuan-Ming Burchett, Rebecca Bramson, Jonathan L. Pinto Sanchez, Maria Ines Stefanolo, Juan Pablo Niveloni, Sonia Surette, Michael G. Murray, Joseph A. Anderson, Robert P. Bercik, Premysl Caminero, Alberto Chirdo, Fernando Gabriel F. Didar, Tohid Verdu, Elena F. |
| author_role |
author |
| author2 |
Galipeau, Heather J. Clarizio, Alexandra V. Wang, Xuanyu Hann, Amber Rueda, Gaston H. Kirtikar, Utkarshini N. Constante, Marco Wulczynski, Mark Su, Hsuan-Ming Burchett, Rebecca Bramson, Jonathan L. Pinto Sanchez, Maria Ines Stefanolo, Juan Pablo Niveloni, Sonia Surette, Michael G. Murray, Joseph A. Anderson, Robert P. Bercik, Premysl Caminero, Alberto Chirdo, Fernando Gabriel F. Didar, Tohid Verdu, Elena F. |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
celiac disease organoid monolayer MHC class II T cell activation |
| topic |
celiac disease organoid monolayer MHC class II T cell activation |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
| dc.description.none.fl_txt_mv |
Background & Aims Intestinal epithelial cell (IEC) damage is a hallmark of celiac disease (CeD); however, its role in gluten-dependent T-cell activation is unknown. We investigated IEC-gluten-T-cell interactions in organoid monolayers expressing human major histocompatibility complex class II (HLA-DQ2.5), which facilitates gluten antigen recognition by CD4+ T cells in CeD. Methods Epithelial major histocompatibility complex class II (MHCII) was determined in active and treated CeD, and in nonimmunized and gluten-immunized DR3-DQ2.5 transgenic mice, lacking mouse MHCII molecules. Organoid monolayers from DR3-DQ2.5 mice were treated with or without interferon (IFN)-γ, and MHCII expression was evaluated by flow cytometry. Organoid monolayers and CD4+ T-cell co-cultures were incubated with gluten, predigested, or not by elastase-producing Pseudomonas aeruginosa or its lasB mutant. T-cell function was assessed based on proliferation, expression of activation markers, and cytokine release in the co-culture supernatants. Results Patients with active CeD and gluten-immunized DR3-DQ2.5 mice demonstrated epithelial MHCII expression. Organoid monolayers derived from gluten-immunized DR3-DQ2.5 mice expressed MHCII, which was upregulated by IFN-γ. In organoid monolayer T-cell co-cultures, gluten increased the proliferation of CD4+ T cells, expression of T-cell activation markers, and the release of interleukin-2, IFN-γ, and interleukin-15 in co-culture supernatants. Gluten metabolized by P aeruginosa, but not the lasB mutant, enhanced CD4+ T-cell proliferation and activation. Conclusions Gluten antigens are efficiently presented by MHCII-expressing IECs, resulting in the activation of gluten-specific CD4+ T cells, which is enhanced by gluten predigestion with microbial elastase. Therapeutics directed at IECs may offer a novel approach for modulating both adaptive and innate immunity in patients with CeD. Fil: Rahmani, Sara. Mc Master University; Canadá Fil: Galipeau, Heather J.. Mc Master University; Canadá Fil: Clarizio, Alexandra V.. Mc Master University; Canadá Fil: Wang, Xuanyu. Mc Master University; Canadá Fil: Hann, Amber. Mc Master University; Canadá Fil: Rueda, Gaston H.. Mc Master University; Canadá Fil: Kirtikar, Utkarshini N.. Mc Master University; Canadá Fil: Constante, Marco. Mc Master University; Canadá Fil: Wulczynski, Mark. Mc Master University; Canadá Fil: Su, Hsuan-Ming. Mc Master University; Canadá Fil: Burchett, Rebecca. Mc Master University; Canadá Fil: Bramson, Jonathan L.. Mc Master University; Canadá Fil: Pinto Sanchez, Maria Ines. Mc Master University; Canadá Fil: Stefanolo, Juan Pablo. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina Fil: Niveloni, Sonia. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina Fil: Surette, Michael G.. Mc Master University; Canadá Fil: Murray, Joseph A.. Division Of Gastroenterology And Hepatology, Department; Estados Unidos Fil: Anderson, Robert P.. Mackay Base Hospital, Mackay, Queensland, Australia;; Australia Fil: Bercik, Premysl. Mc Master University; Canadá Fil: Caminero, Alberto. Mc Master University; Canadá Fil: Chirdo, Fernando Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina Fil: F. Didar, Tohid. Mc Master University; Canadá Fil: Verdu, Elena F.. Mc Master University; Canadá |
| description |
Background & Aims Intestinal epithelial cell (IEC) damage is a hallmark of celiac disease (CeD); however, its role in gluten-dependent T-cell activation is unknown. We investigated IEC-gluten-T-cell interactions in organoid monolayers expressing human major histocompatibility complex class II (HLA-DQ2.5), which facilitates gluten antigen recognition by CD4+ T cells in CeD. Methods Epithelial major histocompatibility complex class II (MHCII) was determined in active and treated CeD, and in nonimmunized and gluten-immunized DR3-DQ2.5 transgenic mice, lacking mouse MHCII molecules. Organoid monolayers from DR3-DQ2.5 mice were treated with or without interferon (IFN)-γ, and MHCII expression was evaluated by flow cytometry. Organoid monolayers and CD4+ T-cell co-cultures were incubated with gluten, predigested, or not by elastase-producing Pseudomonas aeruginosa or its lasB mutant. T-cell function was assessed based on proliferation, expression of activation markers, and cytokine release in the co-culture supernatants. Results Patients with active CeD and gluten-immunized DR3-DQ2.5 mice demonstrated epithelial MHCII expression. Organoid monolayers derived from gluten-immunized DR3-DQ2.5 mice expressed MHCII, which was upregulated by IFN-γ. In organoid monolayer T-cell co-cultures, gluten increased the proliferation of CD4+ T cells, expression of T-cell activation markers, and the release of interleukin-2, IFN-γ, and interleukin-15 in co-culture supernatants. Gluten metabolized by P aeruginosa, but not the lasB mutant, enhanced CD4+ T-cell proliferation and activation. Conclusions Gluten antigens are efficiently presented by MHCII-expressing IECs, resulting in the activation of gluten-specific CD4+ T cells, which is enhanced by gluten predigestion with microbial elastase. Therapeutics directed at IECs may offer a novel approach for modulating both adaptive and innate immunity in patients with CeD. |
| publishDate |
2024 |
| dc.date.none.fl_str_mv |
2024-08 |
| 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 |
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http://hdl.handle.net/11336/266808 Rahmani, Sara; Galipeau, Heather J.; Clarizio, Alexandra V.; Wang, Xuanyu; Hann, Amber; et al.; Gluten-Dependent Activation of CD4+ T Cells by MHC Class II–Expressing Epithelium; W B Saunders Co-Elsevier Inc; Gastroenterology; 167; 6; 8-2024; 1113-1128 0016-5085 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/266808 |
| identifier_str_mv |
Rahmani, Sara; Galipeau, Heather J.; Clarizio, Alexandra V.; Wang, Xuanyu; Hann, Amber; et al.; Gluten-Dependent Activation of CD4+ T Cells by MHC Class II–Expressing Epithelium; W B Saunders Co-Elsevier Inc; Gastroenterology; 167; 6; 8-2024; 1113-1128 0016-5085 CONICET Digital CONICET |
| dc.language.none.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0016508524052119 info:eu-repo/semantics/altIdentifier/doi/10.1053/j.gastro.2024.07.008 |
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info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
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openAccess |
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https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
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application/pdf application/pdf |
| dc.publisher.none.fl_str_mv |
W B Saunders Co-Elsevier Inc |
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W B Saunders Co-Elsevier Inc |
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reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
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dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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