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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...

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Autores principales: Stefanski, Heather E., Xing, Yan, Taylor, Patricia A., Maio, Stefano, Henao-Meija, Jorge, Williams, Adam, Flavell, Richard A., Hollander, Georg A., Blazar, Bruce R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
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.
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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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