title: Breakdown in peripheral tolerance in type 1 diabetes in mice and humans.
abstract: Type 1 Diabetes (T1D), also called juvenile diabetes because of its classically early onset, is considered an autoimmune disease targeting the insulin-producing β cells in the pancreatic islets of Langerhans. T1D reflects a loss of tolerance to tissue self-antigens caused by defects in both central tolerance, which aims at eliminating potentially autoreactive lymphocytes developing in the thymus, and peripheral tolerance, which normally controls autoreactive T cells that escaped the thymus. Like in other autoimmune diseases, the mechanisms leading to T1D are multifactorial and depend on a complex combination of genetic, epigenetic, molecular, and cellular elements that result in the breakdown of peripheral tolerance. In this article, we discuss the contribution of these factors in the development of the autoimmune response targeting pancreatic islets in T1D and the therapeutic strategies currently being explored to correct these defects.
authors.affiliation: UCSF Diabetes Center, University of California at San Francisco, San Francisco, California 94143, USA.
authors.forename: Lukas T
authors.initials: LT
authors.lastname: Jeker
authors.forename: Hélène
authors.initials: H
authors.lastname: Bour-Jordan
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Bluestone
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D060908:CTLA-4 Antigen / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D018450:Disease Progression; D055106:Genome-Wide Association Study; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology; D007515:Islets of Langerhans / Q000502:physiology; D051379:Mice; D016688:Mice, Inbred NOD; D061166:Peripheral Tolerance / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D001324:Autoantigens; D060908:CTLA-4 Antigen; D007376:Interleukin-2