CELIAC DISEASE: PARTICIPATION OF CYTOKINES AND OTHER FACTORS IN THE IMMUNE RESPONSE

Celiac disease (CD) is an autoimmune enteropathy that affects 1% of most populations. Genetic, immunological and environmental factors (the intake of gluten) participate in the establishment and development of the disease. Cells and cytokines make a network of interactions leading to intestinal inflammatory process. IFN-γ is the most potent inducer of transglutaminasa2 (TG2) expressions, acts synergistically with TNF-α, and triggers the upregulation of HLA expression, the secretion of tissue-damaging Metalloproteinases (MMPs) from fibroblasts, the heightened cytotoxicity of Intraepithelial Lymphocytes (IELs) against enterocytes with increased apoptosis and villous flattening. IL-12 and IL-18 have an important suppressive effect on the induction of antigen-specific tolerance and provoke a more vigorous response on challenge. Upregulation of IL-15 expression by epithelial cells and Dendritic Cells (DCs) in the lamina propria seems to contribute to alter signalling properties of the CD8+ intraepithelial lymphocytes and provokes the resistance of human T cells to the suppression by regulatory T cells. IL-15 and IL-21 might also act in concert to disrupt local mechanisms of immune tolerance. Increased expressions of several Th17 related cytokines in patients with active CD have been demonstrated. IL-10 acts by interfering with antigen presentation and induces hyporesponsive in gliadin specific T cells. TGF-β1 expression increased have been observed in the lamina propria of children with intestinal villous atrophy, which appoint its importance in the pathogenesis of CD. In this disease appreciated alteration of immune regulation with predominance of the Th1 and Th17 phenotype cytokines. The profile of mucosal effector cytokines differs between refractory CD and active CD; however, maintain and worsen the inflammatory process. Immune dysregulation, loss of tolerance, increase of pro-inflammatory cytokines and non-suppression of the inflammatory response despite the presence of counter-regulatory mechanisms constitute relevant events in CD.