Immunomodulatory therapy to preserve pancreatic β-cell function in type 1 diabetes

Type 1 diabetes is a common, severe chronic autoimmune disease that is characterized by the progressive and insidious loss of self-tolerance to the insulin-producing pancreatic islet β-cells. This loss of self-tolerance leads to the destruction of β-cells and the development of overt hyperglycaemia at diagnosis. The incidence and prevalence of type 1 diabetes is rapidly increasing worldwide, and this has led to intensive efforts to develop immunotherapies to induce remission of the disease and improve clinical outcomes. Immunotherapy aims to restore self-tolerance, resulting in the downregulation of autoimmune responses to pancreatic self-antigens and arrested ongoing β-cell destruction. When combined with replacement of the lost insulin-producing cells, this may lead to the restoration of euglycaemia. In this review, we discuss the current knowledge of the immunopathogenesis of type 1 diabetes and how this information has been translated into clinical trials. We also discuss next-generation combination immunotherapies that may be administered as adjuvant therapy at time of diagnosis.