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The Thymic Orchestration Involving Aire, miRNAs, and Cell–Cell Interactions during the Induction of Central Tolerance

Developing thymocytes interact sequentially with two distinct structures within the thymus: the cortex and medulla. Surviving single-positive and double-positive thymocytes from the cortex migrate into the medulla, where they interact with medullary thymic epithelial cells (mTECs). These cells ectop...

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Autores principales: Passos, Geraldo Aleixo, Mendes-da-Cruz, Daniella Arêas, Oliveira, Ernna Hérida
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4500981/
https://www.ncbi.nlm.nih.gov/pubmed/26236310
http://dx.doi.org/10.3389/fimmu.2015.00352
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author Passos, Geraldo Aleixo
Mendes-da-Cruz, Daniella Arêas
Oliveira, Ernna Hérida
author_facet Passos, Geraldo Aleixo
Mendes-da-Cruz, Daniella Arêas
Oliveira, Ernna Hérida
author_sort Passos, Geraldo Aleixo
collection PubMed
description Developing thymocytes interact sequentially with two distinct structures within the thymus: the cortex and medulla. Surviving single-positive and double-positive thymocytes from the cortex migrate into the medulla, where they interact with medullary thymic epithelial cells (mTECs). These cells ectopically express a vast set of peripheral tissue antigens (PTAs), a property termed promiscuous gene expression that is associated with the presentation of PTAs by mTECs to thymocytes. Thymocyte clones that have a high affinity for PTAs are eliminated by apoptosis in a process termed negative selection, which is essential for tolerance induction. The Aire gene is an important factor that controls the expression of a large set of PTAs. In addition to PTAs, Aire also controls the expression of miRNAs in mTECs. These miRNAs are important in the organization of the thymic architecture and act as posttranscriptional controllers of PTAs. Herein, we discuss recent discoveries and highlight open questions regarding the migration and interaction of developing thymocytes with thymic stroma, the ectopic expression of PTAs by mTECs, the association between Aire and miRNAs and its effects on central tolerance.
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spelling pubmed-45009812015-07-31 The Thymic Orchestration Involving Aire, miRNAs, and Cell–Cell Interactions during the Induction of Central Tolerance Passos, Geraldo Aleixo Mendes-da-Cruz, Daniella Arêas Oliveira, Ernna Hérida Front Immunol Immunology Developing thymocytes interact sequentially with two distinct structures within the thymus: the cortex and medulla. Surviving single-positive and double-positive thymocytes from the cortex migrate into the medulla, where they interact with medullary thymic epithelial cells (mTECs). These cells ectopically express a vast set of peripheral tissue antigens (PTAs), a property termed promiscuous gene expression that is associated with the presentation of PTAs by mTECs to thymocytes. Thymocyte clones that have a high affinity for PTAs are eliminated by apoptosis in a process termed negative selection, which is essential for tolerance induction. The Aire gene is an important factor that controls the expression of a large set of PTAs. In addition to PTAs, Aire also controls the expression of miRNAs in mTECs. These miRNAs are important in the organization of the thymic architecture and act as posttranscriptional controllers of PTAs. Herein, we discuss recent discoveries and highlight open questions regarding the migration and interaction of developing thymocytes with thymic stroma, the ectopic expression of PTAs by mTECs, the association between Aire and miRNAs and its effects on central tolerance. Frontiers Media S.A. 2015-07-14 /pmc/articles/PMC4500981/ /pubmed/26236310 http://dx.doi.org/10.3389/fimmu.2015.00352 Text en Copyright © 2015 Passos, Mendes-da-Cruz and Oliveira. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Passos, Geraldo Aleixo
Mendes-da-Cruz, Daniella Arêas
Oliveira, Ernna Hérida
The Thymic Orchestration Involving Aire, miRNAs, and Cell–Cell Interactions during the Induction of Central Tolerance
title The Thymic Orchestration Involving Aire, miRNAs, and Cell–Cell Interactions during the Induction of Central Tolerance
title_full The Thymic Orchestration Involving Aire, miRNAs, and Cell–Cell Interactions during the Induction of Central Tolerance
title_fullStr The Thymic Orchestration Involving Aire, miRNAs, and Cell–Cell Interactions during the Induction of Central Tolerance
title_full_unstemmed The Thymic Orchestration Involving Aire, miRNAs, and Cell–Cell Interactions during the Induction of Central Tolerance
title_short The Thymic Orchestration Involving Aire, miRNAs, and Cell–Cell Interactions during the Induction of Central Tolerance
title_sort thymic orchestration involving aire, mirnas, and cell–cell interactions during the induction of central tolerance
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4500981/
https://www.ncbi.nlm.nih.gov/pubmed/26236310
http://dx.doi.org/10.3389/fimmu.2015.00352
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