title: Regulatory mechanisms of immune tolerance in type 1 diabetes and their failures.
abstract: In this brief review we propose to discuss salient data showing the importance of immune regulatory mechanisms, and in particular of Treg, for the control of pathogenic anti-β-cell response in autoimmune diabetes. Disease progression that culminates with the massive destruction of insulin-secreting β-cells and advent of hyperglycemia and glycosuria tightly correlates with a functional deficit in immune regulation. Better dissection of the cellular and molecular mechanisms through which the immune system normally sustains tolerance to "self", and which become defective when autoimmune aggression is overt, is the only direct and robust way to learn how to harness these effectively, so as to restore immune tolerance in patients with insulin-dependent type 1 diabetes. No doubt that regulatory T cells are a privileged mechanism underlying this self-tolerance in the periphery. The discovery of the key role of the transcription factor FoxP3, represented the cornerstone leading to the great advances in the field we are witnessing today. Type 1 diabetes is certainly one of the prototypic T cell-mediated autoimmune diseases where immune regulatory mechanisms relying on specialized subsets of T cells have been the most thoroughly analyzed from the fundamental point of view and also largely exploited in a translational therapeutic perspective.
authors.affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Institutes of Medicine, HIM-730, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
authors.forename: Chantal
authors.initials: C
authors.lastname: Kuhn
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, 75015 Paris, France; INSERM U1151, Institut Necker-Enfants Malades, 75015 Paris, France; CNRS UMR 8253, Institut Necker-Enfants Malades, 75015 Paris, France.
authors.forename: Alix
authors.initials: A
authors.lastname: Besançon
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, 75015 Paris, France; INSERM U1151, Institut Necker-Enfants Malades, 75015 Paris, France; CNRS UMR 8253, Institut Necker-Enfants Malades, 75015 Paris, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lemoine
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, 75015 Paris, France; INSERM U1151, Institut Necker-Enfants Malades, 75015 Paris, France; CNRS UMR 8253, Institut Necker-Enfants Malades, 75015 Paris, France.
authors.forename: Sylvaine
authors.initials: S
authors.lastname: You
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, 75015 Paris, France; INSERM U1151, Institut Necker-Enfants Malades, 75015 Paris, France; CNRS UMR 8253, Institut Necker-Enfants Malades, 75015 Paris, France.
authors.forename: Cindy
authors.initials: C
authors.lastname: Marquet
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, 75015 Paris, France; INSERM U1151, Institut Necker-Enfants Malades, 75015 Paris, France; CNRS UMR 8253, Institut Necker-Enfants Malades, 75015 Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Candon
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, 75015 Paris, France; INSERM U1151, Institut Necker-Enfants Malades, 75015 Paris, France; CNRS UMR 8253, Institut Necker-Enfants Malades, 75015 Paris, France. Electronic address: lucienne.chatenoud@inserm.fr.
authors.forename: Lucienne
authors.initials: L
authors.lastname: Chatenoud
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D017252:CD3 Complex / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D050417:Insulin-Secreting Cells / Q000276:immunology*; D018448:Models, Immunological; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D017252:CD3 Complex; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors
keywords: Autoimmune diabetes; CD3 antibodies; FOXP3; Immune tolerance; pTreg; tTreg