The impact of immune dysregulation on the development of autoimmune gastrointestinal and liver disease.

The intestinal epithelium plays an active immunologic role in preventing the uptake of foreign antigens. Additionally, the intestinal mucosa is an active site for immune suppression through the development of oral tolerance. Dysfunction of any aspect of the intestinal barrier, such as impairment of intestinal tight junctions, immunologic dysregulation or decreased oral tolerance will lead to overstimulation of the immune system upon exposure to foreign antigens and subsequent unregulated chronic intestinal inflammation. This persistent inflammatory activity may potentially predispose the patient to the development of intestinal autoimmune disease. An active immune response possibly directed against intestinal flora has been postulated to be the underlying etiology for inflammatory bowel disease. Failure of oral tolerance is thought predispose a patient to celiac disease and possibly eosinophilic esophagitis. Additionally, an active immunologic response to absorbed antigen may be the underlying etiology for the development of autoimmune liver disease.