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

2007; Rockefeller University Press; Volume: 205; Issue: 1 Linguagem: Inglês

10.1084/jem.20071204

1540-9538

Tamara Matysiak‐Budnik, Ivan Cruz Moura, Michelle Arcos‐Fajardo, Corinne Lebreton, Sandrine Ménard, Céline Candalh, Karima Ben-Khalifa, Christophe Dugave, Houda Tamouza, Guillaume van Niel, Yoram Bouhnik, Dominique Lamarque, Stanislas Chaussade, Georgia Malamut, Christophe Cellier, Nadine Cerf–Bensussan, Renato C. Monteiro, Martine Heyman,

Eosinophilic Esophagitis

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.