Despite high levels of expression in thymic epithelial cells, miR-181a1 and miR-181b1 are not required for thymic development

Heather E Stefanski, Yan Xing, Patricia A Taylor, Stefano Maio, Jorge Henao-Meija, Adam Williams, Richard A. Flavell, Georg A. Hollander, Bruce R Blazar

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbere0198871
JournalPloS one
Volume13
Issue number6
DOIs
StatePublished - Jun 1 2018

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epithelial cells
Epithelial Cells
thymocytes
T-cells
Thymocytes
T-lymphocytes
MicroRNAs
microRNA
mice
T-Lymphocytes
Thymus
Thymus Gland
Genes
stromal cells
Cell Lineage
Stromal Cells
RNA Interference
RNA interference
cell differentiation
Modulators

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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.

In: PloS one, Vol. 13, No. 6, e0198871, 01.06.2018.

Research output: Contribution to journalArticle

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. In: PloS one. 2018 ; Vol. 13, No. 6.
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AU - Maio, Stefano

AU - Henao-Meija, Jorge

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