The Role of the Thymus in the Integrated Evolution of the Recombinase-Dependent Adaptive Immune Response and the Neuroendocrine System

作者：Mottet Marie; Goffinet Lindsay; Beckers Alisson; Bodart Gwennaelle; Morrhaye Gabriel; Kermani Hamid; Renard Chantal; Martens Henri; Geenen Vincent^*

来源：Neuroimmunomodulation, 2011, 18(5): 314-319.

DOI：10.1159/000329498

• Thymus
• Neuroendocrine self-antigens
• Tolerance
• Autoimmunity

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 beta-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.

• 出版日期2011