Article (Scientific journals)
Thymic self-antigens for the design of a negative/tolerogenic self-vaccination against type 1 diabetes.
Geenen, Vincent; Mottet, Marie; Dardenne, Olivier et al.
2010In Current Opinion in Pharmacology, 10, p. 461-472
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Keywords :
Thymus; Type 1 diabetes
Abstract :
[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.
Disciplines :
Endocrinology, metabolism & nutrition
Immunology & infectious disease
Author, co-author :
Geenen, Vincent ;  Université de Liège - ULiège > Centre d'immunologie - Embryologie
Mottet, Marie ;  Université de Liège - ULiège > Centre d'immunologie
Dardenne, Olivier ;  Université de Liège - ULiège > Centre d'immunologie
Kermani, Hamid;  Université de Liège - ULiège > Centre d'Immunologie
Martens, Henri ;  Université de Liège - ULiège > Centre d'immunologie
François, Jean-Marie;  Université de Liège - ULiège
Galleni, Moreno ;  Université de Liège - ULiège > Département des sciences de la vie > Macromolécules biologiques
Hober, Didier;  CHRU Lille > Virologie
Rahmouni, Souad  ;  Université de Liège - ULiège > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén.
Moutschen, Michel  ;  Université de Liège - ULiège > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén.
Language :
English
Title :
Thymic self-antigens for the design of a negative/tolerogenic self-vaccination against type 1 diabetes.
Publication date :
2010
Journal title :
Current Opinion in Pharmacology
ISSN :
1471-4892
eISSN :
1471-4973
Publisher :
Elsevier Science
Volume :
10
Pages :
461-472
Peer reviewed :
Peer Reviewed verified by ORBi
Name of the research project :
Tolediab - Eurothymaide
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
DGTRE - Région wallonne. Direction générale des Technologies, de la Recherche et de l'Énergie [BE]
UE - Union Européenne [BE]
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since 23 October 2010

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