Secretory IgA mediates retrotranscytosis of intact gliadin peptides via the transferrin receptor in celiac disease
| Autor: | Matysiak-Budnik, Tamara, Cruz-Moura, Ivan, 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, Heyman, Martine |
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| Přispěvatelé: | Heyman, Martine, Interactions de l'épithelium intestinal avec le système immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de gastro-entérologie et assistance nutritive, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'Ingénierie et d'Etudes des Protéines, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Compartimentation et dynamique cellulaires (CDC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), Service d'hépato-gastro-entérologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO) |
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
[SDV.IMM] Life Sciences [q-bio]/Immunology
MESH: Glomerulonephritis IGA digestive system MESH: Biopsy MESH: Enterocytes MESH: Receptors Transferrin MESH: Immunoglobulin A intestinal transport MESH: Chromatography High Pressure Liquid MESH: Antigens CD Ussing chamber MESH: Humans MESH: Peptides MESH: Molecular Weight MESH: Models Biological food and beverages nutritional and metabolic diseases MESH: Gliadin MESH: Immunohistochemistry transferrin receptor digestive system diseases gliadin peptides receptor-mediated transcytosis [SDV.IMM]Life Sciences [q-bio]/Immunology celiac disease IgA MESH: Celiac Disease |
| Zdroj: | Journal of Experimental Medicine Journal of Experimental Medicine, 2008, 205 (1), pp.143-54. ⟨10.1084/jem.20071204⟩ |
| ISSN: | 0022-1007 1540-9538 |
| DOI: | 10.1084/jem.20071204⟩ |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
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