Dynamic modulation of thymic microRNAs in response to stress.

<h4>Background</h4>Physiological stress evokes rapid changes in both the innate and adaptive immune response. Immature αβ T cells developing in the thymus are particularly sensitive to stress, with infections and/or exposure to lipopolysaccharide or glucocorticoids eliciting a rapid apop...

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Autores principales:	Serkan Belkaya, Robert L Silge, Ashley R Hoover, Jennifer J Medeiros, Jennifer L Eitson, Amy M Becker, M Teresa de la Morena, Rhonda S Bassel-Duby, Nicolai S C van Oers
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d2b98dd1322f41de97876ff8a1428aca
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spelling	oai:doaj.org-article:d2b98dd1322f41de97876ff8a1428aca2021-11-18T07:34:10ZDynamic modulation of thymic microRNAs in response to stress.1932-620310.1371/journal.pone.0027580https://doaj.org/article/d2b98dd1322f41de97876ff8a1428aca2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22110677/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Physiological stress evokes rapid changes in both the innate and adaptive immune response. Immature αβ T cells developing in the thymus are particularly sensitive to stress, with infections and/or exposure to lipopolysaccharide or glucocorticoids eliciting a rapid apoptotic program. MicroRNAs are a class of small, non-coding RNAs that regulate global gene expression by targeting diverse mRNAs for degradation. We hypothesized that a subset of thymically encoded microRNAs would be stress responsive and modulate thymopoiesis. We performed microRNA profiling of thymic microRNAs isolated from control or stressed thymic tissue obtained from mice. We identified 18 microRNAs that are dysregulated >1.5-fold in response to lipopolysaccharide or the synthetic corticosteroid dexamethasone. These included the miR-17-90 cluster, which have anti-apoptotic functions, and the miR-181 family, which contribute to T cell tolerance. The stress-induced changes in the thymic microRNAs are dynamically and distinctly regulated in the CD4(-)CD8(-), CD4(+)CD8(+), CD4(+)CD8(-), and CD4(-)CD8(+) thymocyte subsets. Several of the differentially regulated murine thymic miRs are also stress responsive in the heart, kidney, liver, brain, and/or spleen. The most dramatic thymic microRNA down modulated is miR-181d, exhibiting a 15-fold reduction following stress. This miR has both similar and distinct gene targets as miR-181a, another member of miR-181 family. Many of the differentially regulated microRNAs have known functions in thymopoiesis, indicating that their dysregulation will alter T cell repertoire selection and the formation of naïve T cells. This data has implications for clinical treatments involving anti-inflammatory steroids, ablation therapies, and provides mechanistic insights into the consequences of infections.Serkan BelkayaRobert L SilgeAshley R HooverJennifer J MedeirosJennifer L EitsonAmy M BeckerM Teresa de la MorenaRhonda S Bassel-DubyNicolai S C van OersPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 11, p e27580 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Serkan Belkaya Robert L Silge Ashley R Hoover Jennifer J Medeiros Jennifer L Eitson Amy M Becker M Teresa de la Morena Rhonda S Bassel-Duby Nicolai S C van Oers Dynamic modulation of thymic microRNAs in response to stress.
description	<h4>Background</h4>Physiological stress evokes rapid changes in both the innate and adaptive immune response. Immature αβ T cells developing in the thymus are particularly sensitive to stress, with infections and/or exposure to lipopolysaccharide or glucocorticoids eliciting a rapid apoptotic program. MicroRNAs are a class of small, non-coding RNAs that regulate global gene expression by targeting diverse mRNAs for degradation. We hypothesized that a subset of thymically encoded microRNAs would be stress responsive and modulate thymopoiesis. We performed microRNA profiling of thymic microRNAs isolated from control or stressed thymic tissue obtained from mice. We identified 18 microRNAs that are dysregulated >1.5-fold in response to lipopolysaccharide or the synthetic corticosteroid dexamethasone. These included the miR-17-90 cluster, which have anti-apoptotic functions, and the miR-181 family, which contribute to T cell tolerance. The stress-induced changes in the thymic microRNAs are dynamically and distinctly regulated in the CD4(-)CD8(-), CD4(+)CD8(+), CD4(+)CD8(-), and CD4(-)CD8(+) thymocyte subsets. Several of the differentially regulated murine thymic miRs are also stress responsive in the heart, kidney, liver, brain, and/or spleen. The most dramatic thymic microRNA down modulated is miR-181d, exhibiting a 15-fold reduction following stress. This miR has both similar and distinct gene targets as miR-181a, another member of miR-181 family. Many of the differentially regulated microRNAs have known functions in thymopoiesis, indicating that their dysregulation will alter T cell repertoire selection and the formation of naïve T cells. This data has implications for clinical treatments involving anti-inflammatory steroids, ablation therapies, and provides mechanistic insights into the consequences of infections.
format	article
author	Serkan Belkaya Robert L Silge Ashley R Hoover Jennifer J Medeiros Jennifer L Eitson Amy M Becker M Teresa de la Morena Rhonda S Bassel-Duby Nicolai S C van Oers
author_facet	Serkan Belkaya Robert L Silge Ashley R Hoover Jennifer J Medeiros Jennifer L Eitson Amy M Becker M Teresa de la Morena Rhonda S Bassel-Duby Nicolai S C van Oers
author_sort	Serkan Belkaya
title	Dynamic modulation of thymic microRNAs in response to stress.
title_short	Dynamic modulation of thymic microRNAs in response to stress.
title_full	Dynamic modulation of thymic microRNAs in response to stress.
title_fullStr	Dynamic modulation of thymic microRNAs in response to stress.
title_full_unstemmed	Dynamic modulation of thymic microRNAs in response to stress.
title_sort	dynamic modulation of thymic micrornas in response to stress.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/d2b98dd1322f41de97876ff8a1428aca
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Dynamic modulation of thymic microRNAs in response to stress.

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