title: Local communication among mucosal immune cells in patients with celiac disease.
abstract: In patients with celiac disease, gluten consumption causes inflammation of the duodenum, and, to a lesser extent, the proximal jejunum. Immune-dominant gluten peptides are modified by the enzyme TG2, leading to their high-affinity binding to HLA-DQ2 or HLA-DQ8 molecules, present in people with a predisposition to celiac disease. Gluten peptide-loaded HLA-DQ2 or HLA-DQ8 molecules are recognized by highly conserved receptors on CD4(+) T cells in the lamina propria. B cells specific for TG2 and modified gluten peptides are also abundant in the lamina propria of patients with celiac disease. In the epithelium, interleukin-15 activates intraepithelial lymphocytes that promote destruction of epithelial cells. However, it is not clear how the immune responses in the lamina propria and the epithelium, separated by a basement membrane, are linked. We review the immune processes that occur in the lamina propria and their potential effects on epithelial pathology in celiac disease.
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: van Bergen
authors.affiliation: Department of Gastroenterology, Free University Medical Center, Amsterdam, The Netherlands.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Mulder
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: M Luisa
authors.initials: ML
authors.lastname: Mearin
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: F.Koning@lumc.nl.
authors.forename: Frits
authors.initials: F
authors.lastname: Koning
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002446:Celiac Disease / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002450:Cell Communication; D019204:GTP-Binding Proteins; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D018928:Immunity, Mucosal; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D015398:Signal Transduction; D011503:Transglutaminases / Q000276:immunology
chemical_list: D001323:Autoantibodies; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; C109756:HLA-DQ8 antigen; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins
keywords: CD4; Celiac Disease; HLA; Immunology; Intestinal Epithelial Cell; Intraepithelial Lymphocyte; T Cell