Gluten peptides are transported across the intestinal epithelium via: retrotranscytosis (i), a protected retrotransport of secretory IgA via transferrin receptor CD71, which allows the entry of intact and thus harmful peptides into the intestinal mucosa; by a transcellular route (ii); or by a paracellular route (iii) as a consequence of impaired mucosal integrity. Gluten peptides might also be sampled by DCs extending their protrusions into the lumen (iv). Deamidation of gluten peptides by tissue transglutaminase (tTG) reinforces presentation of gluten peptides by pDCs to T cells in the context of HLA-DQ2 or HLA-DQ8 molecules. Activated, gluten-reactive Th1 cells produce high levels of proinflammatory cytokines (e.g., IFN-γ and IL-21), which promote fibroblast secretion of MMPs responsible for degradation of ECM and basement membrane, and increase the intraepithelial lymphocyte (IEL) cytotoxicity through interaction between the homodimeric NK-activating receptor NFG2D and the MHC class I–related ligands (MIC), thus leading to epithelial cell apoptosis. IFN-α released by activated pDCs perpetuates the inflammatory reaction by inducing Th1 cells to produce IFN-γ. IL-21 and IL-15 produced by DCs and IECs inhibit TGF-β signaling and Treg function. Additionally, through the production of Th2 cytokines, Th2 cells drive the activation and clonal expansion of B cells, which differentiate into plasma cells producing anti-gliadin and anti–tissue transglutaminase antibodies. The latter have proven to be highly valuable in the diagnosis of celiac disease, as they are present in 98% of celiac patients on a gluten-containing diet.