Article (Scientific journals)
Nouvelles donnees sur la pathogenie du diabete de type 1
Geenen, Vincent; Brilot, F.; Louis, Céline et al.
2005In Revue Médicale de Liège, 60 (5-6, May-Jun), p. 291-6
Peer reviewed
 

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Abstract :
[en] The autoimmune nature of the diabetogenic process and the major contribution of T lymphocytes stand now beyond any doubt. However, despite the identification of the three major type 1-diabetes-related autoantigens (insulin, GAD65 and phosphatase IA-2), the origin of this immune dysregulation still remains unknown. More and more evidence supports a thymic dysfunction in the establishment of central self-tolerance to the insulin family as a crucial factor in the development of the autoimmune response selective of pancreatic insulin-secreting islet beta cells. All the genes of the insulin family (INS, IGF1 and IGF2) are expressed in the thymus network. However, IGF-2 is the dominant member of this family first encountered by T cells in the thymus, and only IGFs control early T-cell differentiation. IGF2 transcription is defective in the thymus in one animal model of type 1 diabetes, the Bio-Breeding (BB) rat. The sequence B9-23, one dominant autoantigen of insulin, and the homologous sequence B11-25 derived from IGF-2 exibit the same affinity and fully compete for binding to DQ8, one class-II major histocompatibility complex (MHC-II) conferring major genetic susceptibility to type 1 diabetes. Compared to insulin B9-23, the presentation of IGF-2 B11-25 to peripheral mononuclear cells (PBMCs) isolated from type 1 diabetic DQ8+ adolescents elicits a regulatory/tolerogenic cytokine profile (*IL-10, *IL-10/IFN-g, *IL-4). Thus, administration of IGF-2 derived self-antigen(s) might constitute a novel form of vaccine/immunotherapy combining both an antagonism for the site of presentation of a susceptible MHC allele, as well as a downstream tolerogenic/regulatory immune response.
Disciplines :
Immunology & infectious disease
Endocrinology, metabolism & nutrition
Author, co-author :
Geenen, Vincent ;  Université de Liège - ULiège > Centre d'immunologie
Brilot, F.
Louis, Céline ;  Université de Liège - ULiège > Centre d'immunologie
Hansenne, Isabelle ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Embryologie
Renard, Cécile ;  Centre Hospitalier Universitaire de Liège - CHU > Rééducation de la parole
Martens, Henri ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Embryologie
Language :
French
Title :
Nouvelles donnees sur la pathogenie du diabete de type 1
Alternative titles :
[en] Importance of a Thymus Dysfunction in the Pathophysiology of Type 1 Diabetes
Publication date :
2005
Journal title :
Revue Médicale de Liège
ISSN :
0370-629X
eISSN :
2566-1566
Publisher :
Université de Liège. Revue Médicale de Liège, Liège, Belgium
Volume :
60
Issue :
5-6, May-Jun
Pages :
291-6
Peer reviewed :
Peer reviewed
Available on ORBi :
since 19 October 2009

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