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Qualitative Changes in Cortical Thymic Epithelial Cells Drive Postpartum Thymic Regeneration

During gestation, sex hormones cause a significant thymic involution which enhances fertility. This thymic involution is rapidly corrected following parturition. As thymic epithelial cells (TECs) are responsible for the regulation of thymopoiesis, we analyzed the sequential phenotypic and transcript...

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Autores principales: Dumont-Lagacé, Maude, Daouda, Tariq, Depoërs, Lucyle, Zumer, Jérémie, Benslimane, Yahya, Brochu, Sylvie, Harrington, Lea, Lemieux, Sébastien, Perreault, Claude
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6974522/
https://www.ncbi.nlm.nih.gov/pubmed/32010151
http://dx.doi.org/10.3389/fimmu.2019.03118
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author Dumont-Lagacé, Maude
Daouda, Tariq
Depoërs, Lucyle
Zumer, Jérémie
Benslimane, Yahya
Brochu, Sylvie
Harrington, Lea
Lemieux, Sébastien
Perreault, Claude
author_facet Dumont-Lagacé, Maude
Daouda, Tariq
Depoërs, Lucyle
Zumer, Jérémie
Benslimane, Yahya
Brochu, Sylvie
Harrington, Lea
Lemieux, Sébastien
Perreault, Claude
author_sort Dumont-Lagacé, Maude
collection PubMed
description During gestation, sex hormones cause a significant thymic involution which enhances fertility. This thymic involution is rapidly corrected following parturition. As thymic epithelial cells (TECs) are responsible for the regulation of thymopoiesis, we analyzed the sequential phenotypic and transcriptomic changes in TECs during the postpartum period in order to identify mechanisms triggering postpartum thymic regeneration. In particular, we performed flow cytometry analyses and deep RNA-sequencing on purified TEC subsets at several time points before and after parturition. We report that pregnancy-induced involution is not caused by loss of TECs since their number does not change during or after pregnancy. However, during pregnancy, we observed a significant depletion of all thymocyte subsets downstream of the double-negative 1 (DN1) differentiation stage. Variations in thymocyte numbers correlated with conspicuous changes in the transcriptome of cortical TECs (cTECs). The transcriptomic changes affected predominantly cTEC expression of Foxn1, its targets and several genes that are essential for thymopoiesis. By contrast, medullary TECs (mTECs) showed very little transcriptomic changes in the early postpartum regenerative phase, but seemed to respond to the expansion of single-positive (SP) thymocytes in the late phase of regeneration. Together, these results show that postpartum thymic regeneration is orchestrated by variations in expression of a well-defined subset of cTEC genes, that occur very early after parturition.
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spelling pubmed-69745222020-01-31 Qualitative Changes in Cortical Thymic Epithelial Cells Drive Postpartum Thymic Regeneration Dumont-Lagacé, Maude Daouda, Tariq Depoërs, Lucyle Zumer, Jérémie Benslimane, Yahya Brochu, Sylvie Harrington, Lea Lemieux, Sébastien Perreault, Claude Front Immunol Immunology During gestation, sex hormones cause a significant thymic involution which enhances fertility. This thymic involution is rapidly corrected following parturition. As thymic epithelial cells (TECs) are responsible for the regulation of thymopoiesis, we analyzed the sequential phenotypic and transcriptomic changes in TECs during the postpartum period in order to identify mechanisms triggering postpartum thymic regeneration. In particular, we performed flow cytometry analyses and deep RNA-sequencing on purified TEC subsets at several time points before and after parturition. We report that pregnancy-induced involution is not caused by loss of TECs since their number does not change during or after pregnancy. However, during pregnancy, we observed a significant depletion of all thymocyte subsets downstream of the double-negative 1 (DN1) differentiation stage. Variations in thymocyte numbers correlated with conspicuous changes in the transcriptome of cortical TECs (cTECs). The transcriptomic changes affected predominantly cTEC expression of Foxn1, its targets and several genes that are essential for thymopoiesis. By contrast, medullary TECs (mTECs) showed very little transcriptomic changes in the early postpartum regenerative phase, but seemed to respond to the expansion of single-positive (SP) thymocytes in the late phase of regeneration. Together, these results show that postpartum thymic regeneration is orchestrated by variations in expression of a well-defined subset of cTEC genes, that occur very early after parturition. Frontiers Media S.A. 2020-01-15 /pmc/articles/PMC6974522/ /pubmed/32010151 http://dx.doi.org/10.3389/fimmu.2019.03118 Text en Copyright © 2020 Dumont-Lagacé, Daouda, Depoërs, Zumer, Benslimane, Brochu, Harrington, Lemieux and Perreault. 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) and the copyright owner(s) 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
Dumont-Lagacé, Maude
Daouda, Tariq
Depoërs, Lucyle
Zumer, Jérémie
Benslimane, Yahya
Brochu, Sylvie
Harrington, Lea
Lemieux, Sébastien
Perreault, Claude
Qualitative Changes in Cortical Thymic Epithelial Cells Drive Postpartum Thymic Regeneration
title Qualitative Changes in Cortical Thymic Epithelial Cells Drive Postpartum Thymic Regeneration
title_full Qualitative Changes in Cortical Thymic Epithelial Cells Drive Postpartum Thymic Regeneration
title_fullStr Qualitative Changes in Cortical Thymic Epithelial Cells Drive Postpartum Thymic Regeneration
title_full_unstemmed Qualitative Changes in Cortical Thymic Epithelial Cells Drive Postpartum Thymic Regeneration
title_short Qualitative Changes in Cortical Thymic Epithelial Cells Drive Postpartum Thymic Regeneration
title_sort qualitative changes in cortical thymic epithelial cells drive postpartum thymic regeneration
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6974522/
https://www.ncbi.nlm.nih.gov/pubmed/32010151
http://dx.doi.org/10.3389/fimmu.2019.03118
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