title: The role of the thymus in the integrated evolution of the recombinase-dependent adaptive immune response and the neuroendocrine system.
abstract: 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 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 the 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.
authors.affiliation: University of Liege Center of Immunology, Institute of Pathology CHU-B23, Liege-Sart Tilman, Belgium.
authors.forename: Marie
authors.initials: M
authors.lastname: Mottet
authors.forename: Lindsay
authors.initials: L
authors.lastname: Goffinet
authors.forename: Alisson
authors.initials: A
authors.lastname: Beckers
authors.forename: Gwennaelle
authors.initials: G
authors.lastname: Bodart
authors.forename: Gabriel
authors.initials: G
authors.lastname: Morrhaye
authors.forename: Hamid
authors.initials: H
authors.lastname: Kermani
authors.forename: Chantal
authors.initials: C
authors.lastname: Renard
authors.forename: Henri
authors.initials: H
authors.lastname: Martens
authors.forename: Vincent
authors.initials: V
authors.lastname: Geenen
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000517:prevention & control; D015551:Autoimmunity / Q000276:immunology; D005075:Biological Evolution; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D009490:Neurosecretory Systems / Q000502:physiology*; D017634:Self Tolerance / Q000276:immunology / Q000502:physiology; D013950:Thymus Gland / Q000166:cytology / Q000502:physiology*