The Gut Immune System and Type 1 Diabetes

Ann N Y Acad Sci. 2002 Apr;958:39-46. doi: 10.1111/j.1749-6632.2002.tb02945.x.

Abstract

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.

MeSH terms

  • Animals
  • Autoimmunity / drug effects
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / physiopathology*
  • Diet
  • Disease Models, Animal
  • Humans
  • Insulin / administration & dosage
  • Insulin / adverse effects
  • Intestines / immunology*
  • Intestines / physiopathology
  • Islets of Langerhans / drug effects
  • Milk / immunology

Substances

  • Insulin