Type 1 diabetes mellitus and its oral tolerance therapy

Abstract

As a T cell-mediated autoimmune disease, type 1 diabetes mellitus (T1DM) is marked by insulin defect resulting from the destruction of pancreatic β-cells. The understanding of various aspects of T1DM, such as its epidemiology, pathobiology, pathogenesis, clinical manifestations, and complications, has been greatly promoted by valuable research performed during the past decades. However, these findings have not been translated into an effective treatment. The ideal treatment should safely repair the destroyed immune balance in a long-lasting manner, preventing or stopping the destruction of β-cells. As a type of immune hypo-responsiveness to the orally administrated antigen, oral tolerance may be induced by enhancement of regulatory T cells (Tregs) or by anergy/deletion of T cells, depending on the dosage of orally administrated antigen. Acting as an antigen-specific immunotherapy, oral tolerance therapy for T1DM has been mainly performed using animal models and some clinical trials have been completed or are still ongoing. Based on the review of the proposed mechanism of the development of T1DM and oral tolerance, we give a current overview of oral tolerance therapy for T1DM conducted in both animal models and clinical trials.

Keywords: Type 1 diabetes mellitus; Immunotherapy; Oral tolerance; Regulatory T cells; Antigen-specific immunotherapy

Core Tip: As an antigen-specific immunotherapy, oral tolerance therapy has shown promise as a new strategy for the prevention and treatment of autoimmune diseases, including type 1 diabetes mellitus. Oral tolerance therapy in type 1 diabetes mellitus has been studied widely for a long time. In order to give a better understanding of these studies performed in animal models as well as in clinical trials, we review the related reports carefully and divide these studies into various categories based on their strategies. This careful review may be useful to guide the future studies.