Reference : Thymic self-antigens for the design of a negative/tolerogenic self-vaccination against t...
Scientific journals : Article
Human health sciences : Endocrinology, metabolism & nutrition
Human health sciences : Immunology & infectious disease
http://hdl.handle.net/2268/74338
Thymic self-antigens for the design of a negative/tolerogenic self-vaccination against type 1 diabetes.
English
Geenen, Vincent mailto [Université de Liège - ULg > > Centre d'immunologie - Embryologie >]
Mottet, Marie mailto [Université de Liège - ULg > > Centre d'immunologie >]
Dardenne, Olivier [Université de Liège - ULg > > Centre d'immunologie >]
Kermani, Hamid [Université de Liège - ULg > Centre d'Immunologie > > >]
Martens, Henri mailto [Université de Liège - ULg > > Centre d'immunologie >]
François, Jean-Marie [Université de Liège - ULg > > > >]
Galleni, Moreno mailto [Université de Liège - ULg > Département des sciences de la vie > Macromolécules biologiques >]
Hober, Didier [CHRU Lille > Virologie > > >]
Rahmouni, Souad mailto [Université de Liège - ULg > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén. >]
Moutschen, Michel mailto [Université de Liège - ULg > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén. >]
2010
Current Opinion in Pharmacology
Elsevier Science
10
461-472
Yes (verified by ORBi)
International
1471-4892
[en] Thymus ; Type 1 diabetes
[en] Before being able to react against infectious non-self antigens, the immune system has to be educated in the recognition and tolerance of neuroendocrine proteins and this critical process takes place only in the thymus. The development of the autoimmune diabetogenic response results from a thymus dysfunction in programming central self-tolerance to pancreatic insulin-secreting islet β cells, leading to the breakdown of immune homeostasis with an enrichment of islet β-cell reactive effector T cells and a deficiency of β-cell specific natural regulatory T cells (nTregs) in the peripheral T-lymphocyte repertoire. Insulin-like growth factor 2 (IGF-2) is the dominant member of the insulin family expressed during fetal life by the thymic epithelium under the control of the autoimmune regulator (AIRE) gene/protein. The very low degree of insulin gene transcription in normal murine and human thymus explains why the insulin protein is poorly tolerogenic as evidenced in many studies, including the failure of all clinical trials that have attempted immune tolerance to islet β cells via various methods of insulin administration. Based on the close homology and cross-tolerance between insulin, the primary T1D autoantigen, and IGF-2, the dominant self-antigen of the insulin family, a novel type of vaccination, so-called “negative/tolerogenic self-vaccination”, is currently being developed for prevention and cure of T1D. If this approach were found to be effective for reprogramming immunological tolerance in T1D, it could pave the way for the design of other self-vaccines against autoimmune endocrine diseases, as well as other organ-specific autoimmune diseases.
Fonds de la Recherche Scientifique (Communauté française de Belgique) - F.R.S.-FNRS ; Région wallonne : Direction générale des Technologies, de la Recherche et de l'Energie - DGTRE ; Union Européenne = European Union - UE = EU
Tolediab - Eurothymaide
Researchers ; Professionals ; Students
http://hdl.handle.net/2268/74338
also: http://hdl.handle.net/2268/71260
10.1016/j.coph.2010.04.005
http://www.sciencedirect.com/science/journal/14714892

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