Immunopathogenesis of Celiac Disease

Resumen

Celiac disease is a chronic infammatory process of the small intestne mediated by the immunesystem which afects genetcally susceptble individuals following the ingeston of prolamins fromwheat and other cereals. The interacton between genetc and environmental factors determinesthe loss of tolerance to gluten and the development of the intestnal lesion, with variable clinicaland functonal repercussions, characterized by an increased number of lymphocytes within theepithelium and the lamina propria, enterocyte apoptosis, the mucosal transformaton, and thepresence of ant-transglutaminase antbodies. The most accepted pathogenesis model for Celiacdisease includes changes in digeston and in the transepithelial transport of gluten, and it isfocused on the mechanisms of adaptve immunity triggered by the stmulaton of CD4+ Tlymphocytes afer recogniton of gluten peptdes deaminated by the tssue transglutaminase(tTG) enzyme in the context of HLA-DQ2/DQ8 molecules, and the producton of proinfammatorycytokines, 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 theepithelial expression of stress molecules and the actvaton of cytotoxic functons byintraepithelial lymphocytes. The interacton between IL15 and its receptor, expressed byepithelial cells, may be also relevant for the inducton of adaptve immunity to gluten. Furtherclarifcaton is needed on several issues, like the passage of gluten into the lamina propria, theactvaton of free tTG, or the mechanisms regulatng the actvity of IL15, among others.