Dynamic modulation of thymic microRNAs in response to stress

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

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Background: 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.

Original languageEnglish (US)
Article numbere27580
JournalPLoS One
Volume6
Issue number11
DOIs
StatePublished - Nov 16 2011

Fingerprint

MicroRNAs
microRNA
stress response
Modulation
T-cells
T-lymphocytes
T-Lymphocytes
lipopolysaccharides
Lipopolysaccharides
Thymus
Small Untranslated RNA
Physiological Stress
thymocytes
Gene Targeting
mice
RNA Stability
Adaptive Immunity
Thymocytes
adrenal cortex hormones
dexamethasone

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Belkaya, S., Silge, R. L., Hoover, A. R., Medeiros, J. J., Eitson, J. L., Becker, A. M., ... van Oers, N. S. C. (2011). Dynamic modulation of thymic microRNAs in response to stress. PLoS One, 6(11), [e27580]. https://doi.org/10.1371/journal.pone.0027580

Dynamic modulation of thymic microRNAs in response to stress. / Belkaya, Serkan; Silge, Robert L.; Hoover, Ashley R.; Medeiros, Jennifer J.; Eitson, Jennifer L.; Becker, Amy M.; de la Morena, M. Teresa; Bassel-Duby, Rhonda S.; van Oers, Nicolai S C.

In: PLoS One, Vol. 6, No. 11, e27580, 16.11.2011.

Research output: Contribution to journalArticle

Belkaya S, Silge RL, Hoover AR, Medeiros JJ, Eitson JL, Becker AM et al. Dynamic modulation of thymic microRNAs in response to stress. PLoS One. 2011 Nov 16;6(11). e27580. https://doi.org/10.1371/journal.pone.0027580
Belkaya, Serkan ; Silge, Robert L. ; Hoover, Ashley R. ; Medeiros, Jennifer J. ; Eitson, Jennifer L. ; Becker, Amy M. ; de la Morena, M. Teresa ; Bassel-Duby, Rhonda S. ; van Oers, Nicolai S C. / Dynamic modulation of thymic microRNAs in response to stress. In: PLoS One. 2011 ; Vol. 6, No. 11.
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