title: Insights into type 1 diabetes from the autoimmune polyendocrine syndromes.
abstract: OBJECTIVE
  Advances in human genetics and investigations in animal models of autoimmune disease have allowed insight into the basic mechanisms of immunologic tolerance. These advances allow us to understand the pathogenesis of type 1 diabetes and other autoimmune diseases as never before. Here, we discuss the tolerance mechanisms of the autoimmune polyendocrine syndromes and their relevance to type 1 diabetes.
  
  
  RESULTS
  Defects in central tolerance with alteration of self-antigen expression levels in the thymus are a potent cause of autoimmunity. Peripheral tolerance defects that alter T-cell activation and signaling also play an important role in the pathogenesis of diabetes and other associated autoimmune disorders, with multiple modest defects working in concert to produce disease. Regulation of the immune response through the action of regulatory T cells is a potent mode of tolerance induction in autoimmunity that is important in type 1 diabetes.
  
  
  CONCLUSIONS
  Rare syndromes of autoimmunity provide a valuable window into the breakdown of tolerance and identify multiple checkpoints that are critical for generation of autoimmunity. Understanding the application of these in type 1 diabetes will allow the development of future immunomodulatory therapies in the treatment and prevention of disease.
authors.affiliation: Diabetes Center, University of California San Francisco, San Francisco, California 94143, USA.
authors.forename: Mickie H
authors.initials: MH
authors.lastname: Cheng
authors.forename: Mark S
authors.initials: MS
authors.lastname: Anderson
mesh_terms: D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D016884:Polyendocrinopathies, Autoimmune / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology