Celiac disease: an immunological jigsaw

Immunity. 2012 Jun 29;36(6):907-19. doi: 10.1016/j.immuni.2012.06.006.

Abstract

Celiac disease (CD) is a chronic enteropathy induced by dietary gluten in genetically predisposed people. The keystone of CD pathogenesis is an adaptive immune response orchestrated by the interplay between gluten and MHC class II HLA-DQ2 and DQ8 molecules. Yet, other factors that impair immunoregulatory mechanisms and/or activate the large population of intestinal intraepithelial lymphocytes (IEL) are indispensable for driving tissue damage. Herein, we summarize our current understanding of the mechanisms and consequences of the undesirable immune response initiated by gluten peptides. We show that CD is a model disease to decipher the role of MHC class II molecules in human immunopathology, to analyze the mechanisms that link tolerance to food proteins and autoimmunity, and to investigate how chronic activation of IEL can lead to T cell lymphomagenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptive Immunity
  • Age of Onset
  • Animals
  • Autoantibodies / biosynthesis
  • Autoantibodies / immunology
  • Autoimmune Diseases / epidemiology
  • Autoimmune Diseases / immunology
  • Celiac Disease / diagnosis
  • Celiac Disease / diet therapy
  • Celiac Disease / epidemiology
  • Celiac Disease / genetics
  • Celiac Disease / immunology*
  • Celiac Disease / pathology
  • Comorbidity
  • Disease Models, Animal
  • Disease Progression
  • Food Hypersensitivity / complications
  • Food Hypersensitivity / immunology
  • GTP-Binding Proteins
  • Genes, MHC Class II
  • Genetic Predisposition to Disease
  • Glutens / adverse effects
  • Glutens / chemistry
  • HLA-D Antigens / immunology
  • Humans
  • Immunoglobulin A / immunology
  • Interleukin-15 / immunology
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / pathology
  • Lymphocyte Activation / genetics
  • Lymphoma, T-Cell / etiology
  • Lymphoma, T-Cell / immunology
  • Mice
  • Models, Immunological*
  • T-Lymphocyte Subsets / immunology
  • Transglutaminases / analysis
  • Transglutaminases / immunology
  • Transglutaminases / physiology
  • Virus Diseases / complications
  • Virus Diseases / immunology

Substances

  • Autoantibodies
  • HLA-D Antigens
  • Immunoglobulin A
  • Interleukin-15
  • Glutens
  • transglutaminase 2
  • Transglutaminases
  • GTP-Binding Proteins