title: Immunomodulatory therapy to preserve pancreatic β-cell function in type 1 diabetes.
abstract: 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.
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, 300 George Street, Suite 353, New Haven, Connecticut 06511, USA. frank.waldron-lynch@yale.edu
authors.forename: Frank
authors.initials: F
authors.lastname: Waldron-Lynch
authors.forename: Kevan C
authors.initials: KC
authors.lastname: Herold
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic / Q000639:trends; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D050417:Insulin-Secreting Cells / Q000276:immunology / Q000502:physiology*; D010179:Pancreas / Q000276:immunology / Q000502:physiology
chemical_list: D007155:Immunologic Factors