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The Gut Immune System and Type 1 Diabetes
Author(s) -
VAARALA OUTI
Publication year - 2002
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2002.tb02945.x
Subject(s) - immune system , autoimmunity , type 1 diabetes , nod mice , insulin , diabetes mellitus , immunology , antibody , autoantibody , insulitis , endocrinology , medicine , biology
A bstract : 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 β7‐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 β 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 β 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 β 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.