Triggers and drivers of autoimmunity: lessons from coeliac disease

Coeliac disease, an inflammatory disease of the small intestine, shares key features with autoimmune disorders, such as susceptibility genes, presence of autoantibodies and T cell-mediated destruction of specific cells. Strikingly, however, continuous exposure to the exogenous dietary antigen gluten and gluten-specific adaptive immunity are required to maintain immunopathology. These observations challenge the notion that autoimmunity requires adaptive immune activation towards self antigens. Using coeliac disease as an example, we propose that other exogenous factors might be identified as drivers of autoimmune processes, in particular when evidence for T cells with specificity for self antigens driving the disease is lacking.