Immunopathogenesis of Celiac Disease

Eduardo Arranz Sanz, E. Montalvillo, J.A. Garrote

Resumen


Celiac disease is a chronic inflammatory process of the small intestine mediated by the immune system which affects genetically susceptible individuals following the ingestion of prolamins from wheat and other cereals. The interaction between genetic and environmental factors determines the loss of tolerance to gluten and the development of the intestinal lesion, with variable clinical and functional repercussions, characterized by an increased number of lymphocytes within the epithelium and the lamina propria, enterocyte apoptosis, the mucosal transformation, and the presence of anti-transglutaminase antibodies. The most accepted pathogenesis model for Celiac disease includes changes in digestion and in the transepithelial transport of gluten, and it is focused on the mechanisms of adaptive immunity triggered by the stimulation of CD4+ T lymphocytes after recognition of gluten peptides deaminated by the tissue transglutaminase (tTG) enzyme in the context of HLA-DQ2/DQ8 molecules, and the production of proinflammatory cytokines, specially IFNγ. Furthermore, gluten has also a direct toxic effect on the epithelium, which depends on innate immunity with IL15 as the central mediator, manifested by the epithelial expression of stress molecules and the activation of cytotoxic functions by intraepithelial lymphocytes. The interaction between IL15 and its receptor, expressed by epithelial cells, may be also relevant for the induction of adaptive immunity to gluten. Further clarification is needed on several issues, like the passage of gluten into the lamina propria, the activation of free tTG, or the mechanisms regulating the activity of IL15, among others.

Palabras clave


celiac, immunopathogenesis

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