The versatile role of gliadin peptides in celiac disease

The link between the gluten component of wheat and celiac disease (CD) was discovered in 1952 by a team of physicians from Birmingham, England. Villous atrophy was described by John W. Paulley in 1954. During the 1960s, other features of CD were elucidated; its hereditary nature was recognized in 1965, and in 1966, dermatitis herpetiformis was linked to gluten sensitivity. Following the discovery of a link between gluten and CD, it was demonstrated that gliadin, one of the two principal protein groups comprising gluten, plays a critical role in CD. It has since become clear that the different and crucial roles of gliadin in CD result from its ability to activate multiple signaling pathways that modulate CD pathology. Most of these pathways involve the host innate and adaptive immune responses, but some pathways are activated when gliadin interacts with the intestinal cellular compartment. This review covers the current knowledge of the role of gliadin peptides in CD disorders that are characterized by intraepithelial T-cells infiltration (IEL), production of autoantibodies, endosomal trafficking, alteration of intestinal barrier function and intestinal cell proliferation. In addition, it examines the ability of these characteristics to determine the main clinicopathological features of gluten sensitivity for the purpose of identifying new strategies, other than maintaining a gluten-free diet, to improve the management of CD patients in the future.