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Secretory IgA mediates retrotranscytosis of intact gliadin peptides via the transferrin receptor in celiac disease

Celiac disease (CD) is an enteropathy resulting from an abnormal immune response to gluten-derived peptides in genetically susceptible individuals. This immune response is initiated by intestinal transport of intact peptide 31-49 (p31-49) and 33-mer gliadin peptides through an unknown mechanism. We...

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Autores principales: Matysiak-Budnik, Tamara, Moura, Ivan Cruz, Arcos-Fajardo, Michelle, Lebreton, Corinne, Ménard, Sandrine, Candalh, Céline, Ben-Khalifa, Karima, Dugave, Christophe, Tamouza, Houda, van Niel, Guillaume, Bouhnik, Yoram, Lamarque, Dominique, Chaussade, Stanislas, Malamut, Georgia, Cellier, Christophe, Cerf-Bensussan, Nadine, Monteiro, Renato C., Heyman, Martine
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2234361/
https://www.ncbi.nlm.nih.gov/pubmed/18166587
http://dx.doi.org/10.1084/jem.20071204
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author Matysiak-Budnik, Tamara
Moura, Ivan Cruz
Arcos-Fajardo, Michelle
Lebreton, Corinne
Ménard, Sandrine
Candalh, Céline
Ben-Khalifa, Karima
Dugave, Christophe
Tamouza, Houda
van Niel, Guillaume
Bouhnik, Yoram
Lamarque, Dominique
Chaussade, Stanislas
Malamut, Georgia
Cellier, Christophe
Cerf-Bensussan, Nadine
Monteiro, Renato C.
Heyman, Martine
author_facet Matysiak-Budnik, Tamara
Moura, Ivan Cruz
Arcos-Fajardo, Michelle
Lebreton, Corinne
Ménard, Sandrine
Candalh, Céline
Ben-Khalifa, Karima
Dugave, Christophe
Tamouza, Houda
van Niel, Guillaume
Bouhnik, Yoram
Lamarque, Dominique
Chaussade, Stanislas
Malamut, Georgia
Cellier, Christophe
Cerf-Bensussan, Nadine
Monteiro, Renato C.
Heyman, Martine
author_sort Matysiak-Budnik, Tamara
collection PubMed
description Celiac disease (CD) is an enteropathy resulting from an abnormal immune response to gluten-derived peptides in genetically susceptible individuals. This immune response is initiated by intestinal transport of intact peptide 31-49 (p31-49) and 33-mer gliadin peptides through an unknown mechanism. We show that the transferrin receptor CD71 is responsible for apical to basal retrotranscytosis of gliadin peptides, a process during which p31-49 and 33-mer peptides are protected from degradation. In patients with active CD, CD71 is overexpressed in the intestinal epithelium and colocalizes with immunoglobulin (Ig) A. Intestinal transport of intact p31-49 and 33-mer peptides was blocked by polymeric and secretory IgA (SIgA) and by soluble CD71 receptors, pointing to a role of SIgA–gliadin complexes in this abnormal intestinal transport. This retrotranscytosis of SIgA–gliadin complexes may promote the entry of harmful gliadin peptides into the intestinal mucosa, thereby triggering an immune response and perpetuating intestinal inflammation. Our findings strongly implicate CD71 in the pathogenesis of CD.
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spelling pubmed-22343612008-07-21 Secretory IgA mediates retrotranscytosis of intact gliadin peptides via the transferrin receptor in celiac disease Matysiak-Budnik, Tamara Moura, Ivan Cruz Arcos-Fajardo, Michelle Lebreton, Corinne Ménard, Sandrine Candalh, Céline Ben-Khalifa, Karima Dugave, Christophe Tamouza, Houda van Niel, Guillaume Bouhnik, Yoram Lamarque, Dominique Chaussade, Stanislas Malamut, Georgia Cellier, Christophe Cerf-Bensussan, Nadine Monteiro, Renato C. Heyman, Martine J Exp Med Articles Celiac disease (CD) is an enteropathy resulting from an abnormal immune response to gluten-derived peptides in genetically susceptible individuals. This immune response is initiated by intestinal transport of intact peptide 31-49 (p31-49) and 33-mer gliadin peptides through an unknown mechanism. We show that the transferrin receptor CD71 is responsible for apical to basal retrotranscytosis of gliadin peptides, a process during which p31-49 and 33-mer peptides are protected from degradation. In patients with active CD, CD71 is overexpressed in the intestinal epithelium and colocalizes with immunoglobulin (Ig) A. Intestinal transport of intact p31-49 and 33-mer peptides was blocked by polymeric and secretory IgA (SIgA) and by soluble CD71 receptors, pointing to a role of SIgA–gliadin complexes in this abnormal intestinal transport. This retrotranscytosis of SIgA–gliadin complexes may promote the entry of harmful gliadin peptides into the intestinal mucosa, thereby triggering an immune response and perpetuating intestinal inflammation. Our findings strongly implicate CD71 in the pathogenesis of CD. The Rockefeller University Press 2008-01-21 /pmc/articles/PMC2234361/ /pubmed/18166587 http://dx.doi.org/10.1084/jem.20071204 Text en Copyright © 2008, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Articles
Matysiak-Budnik, Tamara
Moura, Ivan Cruz
Arcos-Fajardo, Michelle
Lebreton, Corinne
Ménard, Sandrine
Candalh, Céline
Ben-Khalifa, Karima
Dugave, Christophe
Tamouza, Houda
van Niel, Guillaume
Bouhnik, Yoram
Lamarque, Dominique
Chaussade, Stanislas
Malamut, Georgia
Cellier, Christophe
Cerf-Bensussan, Nadine
Monteiro, Renato C.
Heyman, Martine
Secretory IgA mediates retrotranscytosis of intact gliadin peptides via the transferrin receptor in celiac disease
title Secretory IgA mediates retrotranscytosis of intact gliadin peptides via the transferrin receptor in celiac disease
title_full Secretory IgA mediates retrotranscytosis of intact gliadin peptides via the transferrin receptor in celiac disease
title_fullStr Secretory IgA mediates retrotranscytosis of intact gliadin peptides via the transferrin receptor in celiac disease
title_full_unstemmed Secretory IgA mediates retrotranscytosis of intact gliadin peptides via the transferrin receptor in celiac disease
title_short Secretory IgA mediates retrotranscytosis of intact gliadin peptides via the transferrin receptor in celiac disease
title_sort secretory iga mediates retrotranscytosis of intact gliadin peptides via the transferrin receptor in celiac disease
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2234361/
https://www.ncbi.nlm.nih.gov/pubmed/18166587
http://dx.doi.org/10.1084/jem.20071204
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