The thymus in 2013: from a 'vestigial' organ to immunological self-tolerance and autoimmunity
Year: 2014
Type: other
Abstract: The programming of 'neuroendocrine self' occurs in the thymus, a cross-talk organ the emergence of which some 450 millions years ago allowed an integrated and harmonious coevolution between the major systems of cell-to-cell communication, the nervous, endocrine and immune systems.Neuroendocrine self-peptides are secreted by thymic epithelial cells not according to the classic model of neurosecretion, but are processed for the presentation by, or in association with, the major histocompatibility complex proteins.The autoimmune regulator (Aire) gene/protein controls the transcription of neuroendocrine genes in thymic epithelial cells.The presentation of self-peptides derived from endogenous proteins in the thymus is responsible for the negative selection of self-reactive T cells and, paradoxically in the same time, for the positive selection of thymodependant regulatory T (tTreg) cells that can inhibit, in the periphery, those self-reactive T cells that escaped clonal deletion in the thymus.The development of autoimmunity towards endocrine glands first results from a defect in the intrathymic programming of self-tolerance to neuroendocrine functions.This defect may be genetic or acquired, for example during an enteroviral infection.This novel knowledge of normal and pathological functions of the thymus constitutes a solid basis for the development of a novel type of tolerogenic/negative 'self-vaccination' against type 1 diabetes.
Author: Vincent Geenen
Institution: University of Liège
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2133537968