The role of the thymus in integrated evolution of the recombinase-dependent adaptive immune response and the neuroendocrine system

Mottet, Marie; Goffinet, Lindsay; Beckers, Alisson; Bodart, Gwennaëlle; Morrhaye, Gabriel; Kermani, Hamid; RENARD-CHARLET, Jeanne de Chantal; Martens, Henri; Geenen, Vincent

doi:10.1159/000329498

Article (Scientific journals)

The role of the thymus in integrated evolution of the recombinase-dependent adaptive immune response and the neuroendocrine system

Mottet, Marie; Goffinet, Lindsay; Beckers, Alisson et al.

2011 • In Neuroimmunomodulation, 18, p. 314-319

Peer Reviewed verified by ORBi

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https://hdl.handle.net/2268/87539

DOI
10.1159/000329498

PubMed
21952683

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Keywords :

Thymus; Self-tolerance; Neuroendocrine self-antigens; Autoimmunity; Evolution

Abstract :

[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 :

Human health sciences: Multidisciplinary, general & others
Endocrinology, metabolism & nutrition
Immunology & infectious disease

Author, co-author :

Mottet, Marie ; Université de Liège - ULiège > Centre d'immunologie

Goffinet, Lindsay ; Université de Liège - ULiège > Centre d'immunologie

Beckers, Alisson; Université de Liège - ULiège > Centre d'Immunologie

Bodart, Gwennaëlle ; Université de Liège - ULiège > Doct. sc. bioméd. & pharma. (Bologne)

Morrhaye, Gabriel; Université de Liège - ULiège > Centre d'Immunologie

Kermani, Hamid; Université de Liège - ULiège > Centre d'Immunologie

RENARD-CHARLET, Jeanne de Chantal ; Centre Hospitalier Universitaire de Liège - CHU > Endocrinologie clinique

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 :

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
Fonds Léon Fredericq
DGTRE - Région wallonne. Direction générale des Technologies, de la Recherche et de l'Énergie
UE - Union Européenne
EASD - European Association for the Study of Diabetes
JDRF - Juvenile Diabetes Research Foundation

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since 23 March 2011

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