Gliadin triggers autophagy impairment and apoptosis in human enteric glial cells: novel insights in celiac disease pathogenesis

Celiac disease (CD) is a chronic systemic immune-mediated disorder induced in genetically susceptible people by the ingestion of gliadin peptides, the alcohol-soluble fraction of wheat gluten. These peptides, which trigger the inflammatory and immune response underlying CD, exert several biological effects, such as reactive oxygen species (ROS) accumulation, apoptosis of enterocytes and activation of immune cells. This Thesis elucidates the effects of digested gliadin in human enteric glial cells (hEGCs), using an in vitro model based immortalized cell line generated in our laboratory through a protocol of lentiviral transduction. These cells play an important role in gut homeostasis as well as in inflammation/immune response. Despite several studies have investigated the role of EGCs in inflammatory bowel diseases (IBDs), their contribution in the onset of CD is still unknown. The collected results show that gliadin induces increase in ROS and mitochondrial damage, thus leading to a caspase 3/7-mediated cell death. Furthermore, an impairment in autophagy, specifically in the levels of SQSTM1/p62, was observed. Altogether these findings unveil the cytotoxic effects of gliadin in EGCs, suggesting that these cells might play an important role in CD pathogenesis.