Immunopathogenesis of Celiac Disease

Celiac disease is a chronic infammatory process of the small intestne mediated by the immune system which afects genetcally susceptble individuals following the ingeston of prolamins from wheat and other cereals. The interacton between genetc and environmental factors determines the loss of tolerance to gluten and the development of the intestnal lesion, with variable clinical and functonal repercussions, characterized by an increased number of lymphocytes within the epithelium and the lamina propria, enterocyte apoptosis, the mucosal transformaton, and the presence of ant-transglutaminase antbodies. The most accepted pathogenesis model for Celiac disease includes changes in digeston and in the transepithelial transport of gluten, and it is focused on the mechanisms of adaptve immunity triggered by the stmulaton of CD4+ T lymphocytes afer recogniton of gluten peptdes deaminated by the tssue transglutaminase (tTG) enzyme in the context of HLA-DQ2/DQ8 molecules, and the producton of proinfammatory cytokines, specially IFNγ. Furthermore, gluten has also a direct toxic efect on the epithelium, which depends on innate immunity with IL15 as the central mediator, manifested by the epithelial expression of stress molecules and the actvaton of cytotoxic functons by intraepithelial lymphocytes. The interacton between IL15 and its receptor, expressed by epithelial cells, may be also relevant for the inducton of adaptve immunity to gluten. Further clarifcaton is needed on several issues, like the passage of gluten into the lamina propria, the actvaton of free tTG, or the mechanisms regulatng the actvity of IL15, among others.