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
Institut National de la Santé et de la Recherche Médicale (INSERM), U793, Paris 75730, Cedex 15, France.
J Exp Med. 2008 Jan 21;205(1):143-54. doi: 10.1084/jem.20071204. Epub 2007 Dec 31.
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.
乳糜泻（CD）是一种在遗传易感个体中由对麸质衍生肽的异常免疫反应导致的肠病。这种免疫反应由完整的31 - 49肽段（p31 - 49）和33聚体麦醇溶蛋白肽通过未知机制的肠道转运引发。我们发现转铁蛋白受体CD71负责麦醇溶蛋白肽从肠腔顶端到基底的逆向胞吞作用，在此过程中p31 - 49和33聚体肽段受到保护不被降解。在活动性CD患者中，CD71在肠上皮细胞中过度表达并与免疫球蛋白（Ig）A共定位。完整的p31 - 49和33聚体肽段的肠道转运被聚合型和分泌型IgA（SIgA）以及可溶性CD71受体阻断，这表明SIgA - 麦醇溶蛋白复合物在这种异常肠道转运中发挥作用。这种SIgA - 麦醇溶蛋白复合物的逆向胞吞作用可能促进有害的麦醇溶蛋白肽进入肠黏膜，从而引发免疫反应并使肠道炎症持续存在。我们的研究结果有力地表明CD71参与了CD的发病机制。
