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Despite high levels of expression in thymic epithelial cells, miR-181a1 and miR-181b1 are not required for thymic development
MicroRNAs (miRNAs) have been shown to be key modulators of post-transcriptional gene silencing in many cellular processes. In previous studies designed to understand the role of miRNAs in thymic development, we globally deleted miRNA exclusively in thymic epithelial cells (TECs), which are critical...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6021062/ https://www.ncbi.nlm.nih.gov/pubmed/29949604 http://dx.doi.org/10.1371/journal.pone.0198871 |
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author | Stefanski, Heather E. Xing, Yan Taylor, Patricia A. Maio, Stefano Henao-Meija, Jorge Williams, Adam Flavell, Richard A. Hollander, Georg A. Blazar, Bruce R. |
author_facet | Stefanski, Heather E. Xing, Yan Taylor, Patricia A. Maio, Stefano Henao-Meija, Jorge Williams, Adam Flavell, Richard A. Hollander, Georg A. Blazar, Bruce R. |
author_sort | Stefanski, Heather E. |
collection | PubMed |
description | MicroRNAs (miRNAs) have been shown to be key modulators of post-transcriptional gene silencing in many cellular processes. In previous studies designed to understand the role of miRNAs in thymic development, we globally deleted miRNA exclusively in thymic epithelial cells (TECs), which are critical in thymic selection. This resulted in the loss of stromal cells that instruct T cell lineage commitment and affect thymocyte positive selection, required for mature T cell development. Since murine miR-181 is expressed in the thymus and miR-181 deficiency disrupts thymocyte development, we first quantified and thereby demonstrated that miR181a1 and miR181b1 are expressed in purified TECs. By generating mice with TEC targeted loss of miR-181a1 and miR-181b1 expression, we observed that neither TEC cellularity nor thymocyte number nor differentiation was adversely affected. Thus, disrupted thymopoiesis in miR-181 deficient mice was not due to miR-181 loss of expression in TECs. Importantly, in mice with restricted TEC deficiency of miR-181a1 and miR-181b1, there were similar numbers of mature T cells in the periphery in regards to frequencies, differentiation, and function as compared to controls. Moreover miR-181a1 and miR-181b1 were not required for maintenance of thymus integrity over time, as thymic involution was not accelerated in gene-targeted mice. Taken together our data indicate that miR-181a1 and miR-181b1 are dispensable for TEC differentiation, their control of thymocyte development and mature T cell export to and homeostasis within the periphery. |
format | Online Article Text |
id | pubmed-6021062 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-60210622018-07-07 Despite high levels of expression in thymic epithelial cells, miR-181a1 and miR-181b1 are not required for thymic development Stefanski, Heather E. Xing, Yan Taylor, Patricia A. Maio, Stefano Henao-Meija, Jorge Williams, Adam Flavell, Richard A. Hollander, Georg A. Blazar, Bruce R. PLoS One Research Article MicroRNAs (miRNAs) have been shown to be key modulators of post-transcriptional gene silencing in many cellular processes. In previous studies designed to understand the role of miRNAs in thymic development, we globally deleted miRNA exclusively in thymic epithelial cells (TECs), which are critical in thymic selection. This resulted in the loss of stromal cells that instruct T cell lineage commitment and affect thymocyte positive selection, required for mature T cell development. Since murine miR-181 is expressed in the thymus and miR-181 deficiency disrupts thymocyte development, we first quantified and thereby demonstrated that miR181a1 and miR181b1 are expressed in purified TECs. By generating mice with TEC targeted loss of miR-181a1 and miR-181b1 expression, we observed that neither TEC cellularity nor thymocyte number nor differentiation was adversely affected. Thus, disrupted thymopoiesis in miR-181 deficient mice was not due to miR-181 loss of expression in TECs. Importantly, in mice with restricted TEC deficiency of miR-181a1 and miR-181b1, there were similar numbers of mature T cells in the periphery in regards to frequencies, differentiation, and function as compared to controls. Moreover miR-181a1 and miR-181b1 were not required for maintenance of thymus integrity over time, as thymic involution was not accelerated in gene-targeted mice. Taken together our data indicate that miR-181a1 and miR-181b1 are dispensable for TEC differentiation, their control of thymocyte development and mature T cell export to and homeostasis within the periphery. Public Library of Science 2018-06-27 /pmc/articles/PMC6021062/ /pubmed/29949604 http://dx.doi.org/10.1371/journal.pone.0198871 Text en © 2018 Stefanski et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Stefanski, Heather E. Xing, Yan Taylor, Patricia A. Maio, Stefano Henao-Meija, Jorge Williams, Adam Flavell, Richard A. Hollander, Georg A. Blazar, Bruce R. Despite high levels of expression in thymic epithelial cells, miR-181a1 and miR-181b1 are not required for thymic development |
title | Despite high levels of expression in thymic epithelial cells, miR-181a1 and miR-181b1 are not required for thymic development |
title_full | Despite high levels of expression in thymic epithelial cells, miR-181a1 and miR-181b1 are not required for thymic development |
title_fullStr | Despite high levels of expression in thymic epithelial cells, miR-181a1 and miR-181b1 are not required for thymic development |
title_full_unstemmed | Despite high levels of expression in thymic epithelial cells, miR-181a1 and miR-181b1 are not required for thymic development |
title_short | Despite high levels of expression in thymic epithelial cells, miR-181a1 and miR-181b1 are not required for thymic development |
title_sort | despite high levels of expression in thymic epithelial cells, mir-181a1 and mir-181b1 are not required for thymic development |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6021062/ https://www.ncbi.nlm.nih.gov/pubmed/29949604 http://dx.doi.org/10.1371/journal.pone.0198871 |
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