title: Correction of gliadin transport within enterocytes through celiac disease serum.
abstract: Celiac disease (CD) is caused by loss of tolerance toward gluten and related cereal products. The delivery of gliadin peptides (GP) to HLA-DR-positive late endosomes (LE) of enterocytes is required for antigen presentation and tolerance generation. We hypothesized that anti-gliadin antibodies in CD serum modify gliadin transport into LE within enterocytes. CD and control duodenal biopsies were incubated with digests of gluten as well as with serum of CD patients. Lissamin-labeled GP AA31-43 and AA56-68 were endocytozed by Caco-2 cells with serum of CD- or control patients. Colocalization of gliadin with the LE marker LAMP-2 and cathepsin D was determined and quantified on immunofluorescence and immunoelectron microscopical level. Up to 13% of internalized gliadin was located in LE of CD biopsies incubated with CD serum compared with less than 4% in CD biopsies without CD serum as well as in control biopsies. In Caco-2 cells, the colocalization coefficient of GP AA31-43 and LE was 0.82 with CD serum, 0.42 with control serum, and 0.48 with culture medium. Incubation with CD serum can direct GP AA31-43 into LE of enterocytes which is required for antigen presentation.
authors.affiliation: Department of Pediatrics, Justus-Liebig-University Giessen, 35392 Giessen, Germany.
authors.forename: Nico
authors.initials: N
authors.lastname: Lübbing
authors.forename: Maria-Vittoria
authors.initials: MV
authors.lastname: Barone
authors.forename: Silvia
authors.initials: S
authors.lastname: Rudloff
authors.forename: Riccardo
authors.initials: R
authors.lastname: Troncone
authors.forename: Salvatore
authors.initials: S
authors.lastname: Auricchio
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Zimmer
mesh_terms: D017951:Antigen Presentation / Q000276:immunology; D001692:Biological Transport / Q000276:immunology; D001706:Biopsy; D018938:Caco-2 Cells; D002446:Celiac Disease / Q000097:blood* / Q000276:immunology; D002648:Child; D003470:Culture Media / Q000737:chemistry; D004386:Duodenum / Q000166:cytology / Q000378:metabolism / Q000601:surgery; D011992:Endosomes / Q000378:metabolism; D020895:Enterocytes / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D005903:Gliadin / Q000235:genetics / Q000378:metabolism*; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D008297:Male; D010455:Peptides / Q000235:genetics / Q000378:metabolism
chemical_list: D003470:Culture Media; D006684:HLA-DR Antigens; D010455:Peptides; D005903:Gliadin