The gut immune system and type 1 diabetes.
Accumulating data suggest that the gut immune system plays a role in the development of autoimmune diabetes: (1) Diet modifies the incidence of autoimmune diabetes and the phenotype of the islet-infiltrating T cells in the animal models of human type 1 diabetes; (2) gut-associated homing receptor beta7-integrin is found on the islet-infiltrating T cells in both human type 1 diabetes and in the animal models of autoimmune diabetes; (3) mesenterial lymphocytes from young NOD mice are able to transfer diabetes to healthy recipients; (4) autoantigen feeding modifies the disease development in the animal models (prevents or accelerates autoimmune diabetes). In humans, a link between the gut immune system and type 1 diabetes has also been suggested. Early introduction of cow milk formulas in infancy may increase the risk of type 1 diabetes. We have demonstrated that primary immunization to a beta cell-specific autoantigen, insulin, occurs in the gut by exposure to cow milk formulas, which contain immunogenic bovine insulin. The induced antibody and T cell responses to bovine insulin cross-react with human insulin. In children at genetic risk who developed beta cell autoimmunity, bovine insulin-binding antibodies increased during follow-up in contrast to autoantibody-negative children. This suggests that insulin-specific immune response induced by dietary insulin may not be controlled in children prone to beta cell autoimmunity. The gut immune system has a key role in controlling insulin-specific immunity induced by dietary insulin. Indeed, indications for aberrant function of the gut immune system have been reported in type 1 diabetes, such as intestinal immune activation and increased intestinal permeability. Research on the gut immune system in human type 1 diabetes is needed to reveal the role of oral immunity in this disease.
Vaarala
Outi
O
Department of Molecular Medicine, National Public Health Institute, Biomedicum, 00251 Helsinki, Finland. outi.vaarala@ktl.fi
D000818:Animals; D015551:Autoimmunity / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000503:physiopathology*; D004032:Diet; D004195:Disease Models, Animal; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects; D007422:Intestines / Q000276:immunology* / Q000503:physiopathology; D007515:Islets of Langerhans / Q000187:drug effects; D008892:Milk / Q000276:immunology
D007328:Insulin