Interplay between the toxic alpha-gliadin peptide 31-43 and type 2 transglutaminase enzyme in Celiac Disease

Introduction: Celiac disease (CD) is a widespread enteropathy triggered by a diet containing cereals with gliadins in genetically predisposed individuals. Alpha-gliadin peptide 31–43 (p31-43) is considered the main responsible of the innate immune response in CD patients and type 2 transglutaminase (TG2) enzyme is involved in CD by enhancing gliadin immunogenicity. Evidence has been reported on a role of TG2 in modulate p31-43 uptake by intestinal cells; indeed, antibodies to TG2 specifically reduced both p31-43 uptake by cells and its biological activity. However, little is known about molecular mechanism underlying p31-43 uptake. We aim to investigate the effect of p31-43 on TG2 expression and activity into a model of skin-derived CD fibroblasts; furthermore we investigate whether cell surfaceTG2 could be directly responsible of p31-43 translocation into intestinal cells.