[en] Before being able to react against infectious non-self antigens, the immune system has to be educated in recognition and tolerance of neuroendocrine self-proteins. This sophisticated educational process takes place only in the thymus. The development of an autoimmune response directed to neuroendocrine glands has been shown to result from a thymus dysfunction in programming immunological self-tolerance to neuroendocrine-related antigens. This thymus dysfunction leads to a breakdown of immune homeostasis with an enrichment of ‘forbidden’ self-reactive T cells and a deficiency in self-antigen specific natural regulatory T cells (nTreg) in the peripheral T-lymphocyte repertoire. A large number of neuroendocrine self-antigens are expressed by the thymic epithelium, under the control of the autoimmune regulator (AIRE) gene/protein in the medulla. Based on the close homology and cross-tolerance between thymic type 1 diabetes-related self-antigens and peripheral antigens targeted in β cells by autoimmunity, a novel type of vaccination is currently developed for prevention and cure of type 1 diabetes. If this approach were found to be effective in reprogramming immunological tolerance that is absent or broken in this disease, it could pave the way for the design of negative/tolerogenic self-vaccines against other endocrine and organ-specific autoimmune disorders.
Disciplines :
Immunology & infectious disease Human health sciences: Multidisciplinary, general & others Endocrinology, metabolism & nutrition
Author, co-author :
Mottet, Marie ; Université de Liège - ULiège > Centre d'immunologie
Martens, Henri ; Université de Liège - ULiège > Centre d'immunologie
Geenen, Vincent ; Université de Liège - ULiège > Centre d'immunologie
Language :
English
Title :
The role of the thymus in integrated evolution of the recombinase-dependent adaptive immune response and the neuroendocrine system
Publication date :
2011
Journal title :
Neuroimmunomodulation
ISSN :
1021-7401
eISSN :
1423-0216
Publisher :
S. Karger, Basel, Switzerland
Special issue title :
Neuroendocrinology of the thymus
Volume :
18
Pages :
314-319
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] Fonds Léon Fredericq [BE] DGTRE - Région wallonne. Direction générale des Technologies, de la Recherche et de l'Énergie [BE] UE - Union Européenne [BE] EASD - European Association for the Study of Diabetes [DE] JDRF - Juvenile Diabetes Research Foundation [CA]
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