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Transgenic Expression of MicroRNA-181d Augments the Stress-Sensitivity of CD4(+)CD8(+) Thymocytes

Physiological stress resulting from infections, trauma, surgery, alcoholism, malnutrition, and/or pregnancy results in a substantial depletion of immature CD4(+)CD8(+) thymocytes. We previously identified 18 distinct stress-responsive microRNAs (miRs) in the thymus upon systemic stress induced by li...

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Autores principales: Belkaya, Serkan, van Oers, Nicolai S. C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3887031/
https://www.ncbi.nlm.nih.gov/pubmed/24416377
http://dx.doi.org/10.1371/journal.pone.0085274
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author Belkaya, Serkan
van Oers, Nicolai S. C.
author_facet Belkaya, Serkan
van Oers, Nicolai S. C.
author_sort Belkaya, Serkan
collection PubMed
description Physiological stress resulting from infections, trauma, surgery, alcoholism, malnutrition, and/or pregnancy results in a substantial depletion of immature CD4(+)CD8(+) thymocytes. We previously identified 18 distinct stress-responsive microRNAs (miRs) in the thymus upon systemic stress induced by lipopolysaccharide (LPS) or the synthetic glucocorticoid, dexamethasone (Dex). MiRs are short, non-coding RNAs that play critical roles in the immune system by targeting diverse mRNAs, suggesting that their modulation in the thymus in response to stress could impact thymopoiesis. MiR-181d is one such stress-responsive miR, exhibiting a 15-fold down-regulation in expression. We utilized both transgenic and gene-targeting approaches to study the impact of miR-181d on thymopoiesis under normal and stress conditions. The over-expression of miR-181d in developing thymocytes reduced the total number of immature CD4(+)CD8(+) thymocytes. LPS or Dex injections caused a 4-fold greater loss of these cells when compared with the wild type controls. A knockout mouse was developed to selectively eliminate miR-181d, leaving the closely spaced and contiguous family member miR-181c intact. The targeted elimination of just miR-181d resulted in a thymus stress-responsiveness similar to wild-type mice. These experiments suggest that one or more of three other miR-181 family members have overlapping or compensatory functions. Gene expression comparisons of thymocytes from the wild type versus transgenic mice indicated that miR-181d targets a number of stress, metabolic, and signaling pathways. These findings demonstrate that selected miRs enhance stress-mediated thymic involution in vivo.
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spelling pubmed-38870312014-01-10 Transgenic Expression of MicroRNA-181d Augments the Stress-Sensitivity of CD4(+)CD8(+) Thymocytes Belkaya, Serkan van Oers, Nicolai S. C. PLoS One Research Article Physiological stress resulting from infections, trauma, surgery, alcoholism, malnutrition, and/or pregnancy results in a substantial depletion of immature CD4(+)CD8(+) thymocytes. We previously identified 18 distinct stress-responsive microRNAs (miRs) in the thymus upon systemic stress induced by lipopolysaccharide (LPS) or the synthetic glucocorticoid, dexamethasone (Dex). MiRs are short, non-coding RNAs that play critical roles in the immune system by targeting diverse mRNAs, suggesting that their modulation in the thymus in response to stress could impact thymopoiesis. MiR-181d is one such stress-responsive miR, exhibiting a 15-fold down-regulation in expression. We utilized both transgenic and gene-targeting approaches to study the impact of miR-181d on thymopoiesis under normal and stress conditions. The over-expression of miR-181d in developing thymocytes reduced the total number of immature CD4(+)CD8(+) thymocytes. LPS or Dex injections caused a 4-fold greater loss of these cells when compared with the wild type controls. A knockout mouse was developed to selectively eliminate miR-181d, leaving the closely spaced and contiguous family member miR-181c intact. The targeted elimination of just miR-181d resulted in a thymus stress-responsiveness similar to wild-type mice. These experiments suggest that one or more of three other miR-181 family members have overlapping or compensatory functions. Gene expression comparisons of thymocytes from the wild type versus transgenic mice indicated that miR-181d targets a number of stress, metabolic, and signaling pathways. These findings demonstrate that selected miRs enhance stress-mediated thymic involution in vivo. Public Library of Science 2014-01-09 /pmc/articles/PMC3887031/ /pubmed/24416377 http://dx.doi.org/10.1371/journal.pone.0085274 Text en © 2014 Belkaya, van Oers http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Belkaya, Serkan
van Oers, Nicolai S. C.
Transgenic Expression of MicroRNA-181d Augments the Stress-Sensitivity of CD4(+)CD8(+) Thymocytes
title Transgenic Expression of MicroRNA-181d Augments the Stress-Sensitivity of CD4(+)CD8(+) Thymocytes
title_full Transgenic Expression of MicroRNA-181d Augments the Stress-Sensitivity of CD4(+)CD8(+) Thymocytes
title_fullStr Transgenic Expression of MicroRNA-181d Augments the Stress-Sensitivity of CD4(+)CD8(+) Thymocytes
title_full_unstemmed Transgenic Expression of MicroRNA-181d Augments the Stress-Sensitivity of CD4(+)CD8(+) Thymocytes
title_short Transgenic Expression of MicroRNA-181d Augments the Stress-Sensitivity of CD4(+)CD8(+) Thymocytes
title_sort transgenic expression of microrna-181d augments the stress-sensitivity of cd4(+)cd8(+) thymocytes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3887031/
https://www.ncbi.nlm.nih.gov/pubmed/24416377
http://dx.doi.org/10.1371/journal.pone.0085274
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