title: Autoimmune Diabetes: An Overview of Experimental Models and Novel Therapeutics.
abstract: Type 1 diabetes (T1D) results from a chronic and selective destruction of insulin-secreting β-cells within the islets of Langerhans of the pancreas by autoreactive CD4(+) and CD8(+) T lymphocytes. The use of animal models of T1D was instrumental for deciphering the steps of the autoimmune process leading to T1D. The non-obese diabetic (NOD) mouse and the bio-breeding (BB) rat spontaneously develop the disease similar to the human pathology in terms of the immune responses triggering autoimmune diabetes and of the genetic and environmental factors influencing disease susceptibility. The generation of genetically modified models allowed refining our understanding of the etiology and the pathogenesis of the disease. In the present review, we provide an overview of the experimental models generated and used to gain knowledge on the molecular and cellular mechanisms underlying the breakdown of self-tolerance in T1D and the progression of the autoimmune response. Immunotherapeutic interventions designed in these animal models and translated into the clinical arena in T1D patients will also be discussed.
authors.affiliation: INSERM U1151, Hôpital Necker-Enfants Malades, 149 Rue de Sevres, 75015, Paris, France. sylvaine.you@inserm.fr.|CNRS UMR 8253, Hôpital Necker-Enfants Malades, Paris, France. sylvaine.you@inserm.fr.|Université Paris Descartes, Sorbonne Paris Cité, 75475, Paris, France. sylvaine.you@inserm.fr.
authors.forename: Sylvaine
authors.initials: S
authors.lastname: You
authors.affiliation: INSERM U1151, Hôpital Necker-Enfants Malades, 149 Rue de Sevres, 75015, Paris, France.|CNRS UMR 8253, Hôpital Necker-Enfants Malades, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, 75475, Paris, France.
authors.forename: Lucienne
authors.initials: L
authors.lastname: Chatenoud
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D001947:Breeding; D003921:Diabetes Mellitus, Experimental; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000628:therapy; D004195:Disease Models, Animal; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D007167:Immunotherapy / Q000379:methods; D016219:Immunotherapy, Adoptive / Q000379:methods; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D051381:Rats; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D014182:Transplantation, Autologous
chemical_list: D007155:Immunologic Factors
keywords: Autoantigens; Autoimmunity; Experimental models; Immunotherapies; NOD mice; Pancreatic beta-cells; T lymphocytes; Type 1 diabetes