1. The presentation of neuroendocrine self‐peptides in the thymus: an essential event for individual life and vertebrate survival
- Author
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Vincent Geenen, Hela Jaïdane, Henri Martens, Caroline Collée, Aymen Halouani, Chantal Renard, Philippe Ledent, Charlotte Trussart, Hélène Michaux, and Marc Daukandt
- Subjects
tolerogenic ,0301 basic medicine ,T cell ,Immunology ,Reviews ,Thymus Gland ,Review ,Biology ,medicine.disease_cause ,Major histocompatibility complex ,General Biochemistry, Genetics and Molecular Biology ,Autoimmunity ,03 medical and health sciences ,Negative selection ,0302 clinical medicine ,History and Philosophy of Science ,Antigen ,thymus ,self‐tolerance ,Immune Tolerance ,medicine ,Animals ,Humans ,reverse ,Transcription factor ,Zinc finger ,General Neuroscience ,autoimmunity ,Cell Biology ,self‐peptide ,self‐vaccine ,Autoimmune regulator ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,biology.protein ,Peptides ,Neuroscience ,030215 immunology - Abstract
Confirming Burnet's early hypothesis, elimination of self‐reactive T cells in the thymus was demonstrated in the late 1980s, and an important question immediately arose about the nature of the self‐peptides expressed in the thymus. Many genes encoding neuroendocrine‐related and tissue‐restricted antigens (TRAs) are transcribed in thymic epithelial cells (TECs). They are then processed for presentation by proteins of the major histocompatibility complex (MHC) expressed by TECs and thymic dendritic cells. MHC presentation of self‐peptides in the thymus programs self‐tolerance by two complementary mechanisms: (1) negative selection of self‐reactive “forbidden” T cell clones starting already in fetal life, and (2) generation of self‐specific thymic regulatory T lymphocytes (tTreg cells), mainly after birth. Many studies, including the discovery of the transcription factors autoimmune regulator (AIRE) and fasciculation and elongation protein zeta family zinc finger (FEZF2), have shown that a defect in thymus central self‐tolerance is the earliest event promoting autoimmunity. AIRE and FEZF2 control the level of transcription of many neuroendocrine self‐peptides and TRAs in the thymic epithelium. Furthermore, AIRE and FEZF2 mutations are associated with the development of autoimmunity in peripheral organs. The discovery of the intrathymic presentation of self‐peptides has revolutionized our knowledge of immunology and is opening novel avenues for prevention/treatment of autoimmunity., Presentation of self‐peptides in the thymus is the basic mechanism that underlies T cell differentiation, negative selection of self‐reactive T cell clones, and generation of tTreg cells. There is no doubt that thymus‐based novel strategies could alleviate in the future the weight of so many known and still unknown autoimmune diseases that remain the heavy tribute, mainly paid by mankind, for the performance and extreme diversity of its highly complex adaptive immunity.
- Published
- 2019