Immunopathology of Celiac Disease

Celiac disease (CD) is a T cell-mediated intestinal disorder induced by dietary gluten in genetically susceptible individuals. It is a prototypic example of how the interaction between predisposing genes (human leukocyte antigen (HLA) and non-HLA genes) and the environment (gluten) can lead to the development of complex inflammatory disorders. Although anti-gluten CD4⁺ T cells are central in all aspects of CD pathogenesis, from the loss of oral tolerance to the generation of antibodies, intraepithelial cytotoxic CD8⁺ T lymphocytes are indispensable to promote intestinal tissue destruction. Furthermore, posttranslational modifications mediated by tissue transglutaminase-2 appear to be key in the initiation and/or amplification of anti-gluten T cell immunity. Despite many advances in our understanding of CD pathophysiology, how distinct immunological pathways cooperate to promote the destruction of intestinal epithelial cells is not yet fully understood. Here we summarize our current knowledge on the immunobiology of CD and discuss future research perspectives.