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The presentation of neuroendocrine self‐peptides in the thymus: an essential event for individual life and vertebrate survival

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‐restricte...

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Autores principales: Geenen, Vincent, Trussart, Charlotte, Michaux, Hélène, Halouani, Aymen, Jaïdane, Hela, Collée, Caroline, Renard, Chantal, Daukandt, Marc, Ledent, Philippe, Martens, Henri
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899491/
https://www.ncbi.nlm.nih.gov/pubmed/31008523
http://dx.doi.org/10.1111/nyas.14089
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author Geenen, Vincent
Trussart, Charlotte
Michaux, Hélène
Halouani, Aymen
Jaïdane, Hela
Collée, Caroline
Renard, Chantal
Daukandt, Marc
Ledent, Philippe
Martens, Henri
author_facet Geenen, Vincent
Trussart, Charlotte
Michaux, Hélène
Halouani, Aymen
Jaïdane, Hela
Collée, Caroline
Renard, Chantal
Daukandt, Marc
Ledent, Philippe
Martens, Henri
author_sort Geenen, Vincent
collection PubMed
description 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 (tT(reg) 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.
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spelling pubmed-68994912019-12-19 The presentation of neuroendocrine self‐peptides in the thymus: an essential event for individual life and vertebrate survival Geenen, Vincent Trussart, Charlotte Michaux, Hélène Halouani, Aymen Jaïdane, Hela Collée, Caroline Renard, Chantal Daukandt, Marc Ledent, Philippe Martens, Henri Ann N Y Acad Sci Reviews 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 (tT(reg) 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. John Wiley and Sons Inc. 2019-04-22 2019-11 /pmc/articles/PMC6899491/ /pubmed/31008523 http://dx.doi.org/10.1111/nyas.14089 Text en © 2019 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals, Inc. on behalf of New York Academy of Sciences This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Reviews
Geenen, Vincent
Trussart, Charlotte
Michaux, Hélène
Halouani, Aymen
Jaïdane, Hela
Collée, Caroline
Renard, Chantal
Daukandt, Marc
Ledent, Philippe
Martens, Henri
The presentation of neuroendocrine self‐peptides in the thymus: an essential event for individual life and vertebrate survival
title The presentation of neuroendocrine self‐peptides in the thymus: an essential event for individual life and vertebrate survival
title_full The presentation of neuroendocrine self‐peptides in the thymus: an essential event for individual life and vertebrate survival
title_fullStr The presentation of neuroendocrine self‐peptides in the thymus: an essential event for individual life and vertebrate survival
title_full_unstemmed The presentation of neuroendocrine self‐peptides in the thymus: an essential event for individual life and vertebrate survival
title_short The presentation of neuroendocrine self‐peptides in the thymus: an essential event for individual life and vertebrate survival
title_sort presentation of neuroendocrine self‐peptides in the thymus: an essential event for individual life and vertebrate survival
topic Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899491/
https://www.ncbi.nlm.nih.gov/pubmed/31008523
http://dx.doi.org/10.1111/nyas.14089
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