Celiac Disease: Molecular Basis

Abstract

Celiac disease (CD) is an inflammatory and multifactorial disorder triggered by cereal gluten in genetically predisposed individuals. CD has several clinical and histological forms characterised by different grade of small intestinal inflammation. Several studies have demonstrated the key role of adaptive CD4+ T lymphocytes in gluten‐dependent enteropathy, although it has been clear that the intraepithelial CD8+ T lymphocytes of innate immunity, highly infiltrating CD mucosa, are pivotal in the induction of intestinal mucosa alteration and malfunction. Recent evidences also highlighted how adaptive CD8+ T lymphocytes restricted by HLA class I molecules contribute to the enterocytes damage through a TCR‐dependent cytotoxic activity. The recent findings on the involvement of HLA class I genes in CD susceptibility are also discussed. Key Concepts Celiac disease is an immune‐mediated disorder triggered by dietary gluten. Enteropathy is the main form of celiac disease, but extra‐intestinal manifestations are also frequent. Celiac disease has autoimmune features characterised by the production of antitissue transglutaminase antibodies, with high diagnostic relevance. Gluten‐reactive CD4+ T cells are key players as pathogenic T helper cells. Cytotoxic CD8+ T cells, of both innate and adaptive branches, are involved in the intestinal villous atrophy. The current therapy is the avoidance of gluten from the diet.