Pathogenesis of Celiac Disease

Celia Escudero-Hernández, Jose Antonio Garrote, Eduardo Arranz


Celiac disease is a chronic, immune-mediated inflammatory disorder of the small intestine that affects genetically susceptible individuals after ingestion of gluten proteins in wheat, barley and rye cereals. The interaction of genetic and environmental factors leads to loss of tolerance to these proteins and to the development of intestinal lesions characterised by intraepithelial lymphocytosis, enterocyte destruction, mucosal remodelling and the presence of auto-antibodies to the enzyme tissue transglutaminase (TG2). The most widely-accepted pathogenic model includes altered digestion and transport of gluten across the epithelium. This focuses on adaptive immunity mechanisms that depend on stimulation of gluten-reactive CD4+ T cells, which are capable of recognising TG2-deamidated gluten peptides presented by HLA-DQ2/DQ8 molecules, and proinflammatory cytokine production, especially interferon (IFN)-g. Furthermore, in the innate immune response, gluten has a direct toxic effect on the epithelium, in which the main mediator is interleukin (IL)-15. This is manifested by the expression of stress molecules in enterocytes and activation of CD8+ intraepithelial T-cell cytotoxic function. Some aspects still need to be clarified, especially regarding the nonspecific interaction between gluten and epithelial cells, passage of gluten peptides into the lamina propria mucosa, TG2 activation, mechanisms that regulate IL-15 expression, and auto-antibody production.

Palabras clave

tolerance breakage, transepithelial transport, IL15, IFNγ, Intraepithelial lymphocytosis, CD8+ T Lymphocytes, TG2, HLA-DQ

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