Figure 1.

Key steps in CeD pathogenesis. Gluten peptides containing T-cell epitopes resist gastrointestinal degradation. tTG catalyses the deamidation of gluten peptides, which can then bind more efficiently to the disease-relevant HLA-DQ molecules on APCs. Activated gluten-specific CD4+ T cells secrete a variety of pro-inflammatory cytokines such as IFN-γ and IL-21 that contribute to the intestinal lesion and promote activation of IELs and stimulate B-cell responses. Activated IELs transform into cytolytic NK-like cells that mediate destruction of enterocytes expressing stress signals. IL-15 renders effector T cells resistant to the suppressive effects of Tregs and, in the lamina propria, endows mucosal DCs with inflammatory properties promoting pro-inflammatory responses and preventing Treg differentiation.