New insights on genes, gluten and immunopathogenesis of celiac disease

Celiac disease (CeD) is a gluten-induced enteropathy that develops in genetically susceptible individuals on consumption of cereal gluten proteins. It is a unique complex immune disorder to study as the driving antigen is known and the tissue targeted by the immune reaction can be interrogated. This review integrates findings gained from genetic, biochemical and immunological studies, which together have revealed mechanisms of gluten peptide modification and HLA binding thereby enabling a maladapted anti-gluten immune response. Observations in human samples combined with experimental mouse models have revealed that the gluten-induced immune response involves both CD4+ T cells, cytotoxic CD8+ T cells, and B cells whose cross-talks are critical for the tissue damaging response. The emergence of high throughput technologies is increasing our understanding of the phenotype, location and presumably function of the gluten-specific cells, all required to identify novel therapeutic targets and strategies for CeD.