The miR-17 ∼ 92a cluster of microRNAs is required for the fitness of Foxp3+ regulatory T cells

PLoS One. 2014 Feb 11;9(2):e88997. doi: 10.1371/journal.pone.0088997. eCollection 2014.

Abstract

By genetic inactivation of key microRNA biogenesis enzymes, we and others have previously demonstrated the critical requirement of the microRNA pathway for the differentiation and function of Foxp3(+) regulatory T cells. In this study, we identified members of the miR-17 ∼ 92a cluster of microRNAs to be enriched in regulatory T cells. To investigate the function of this microRNA cluster, we deleted the gene specifically in Foxp3(+) cells in mice. We found that miR-17 ∼ 92a is required for the fitness of regulatory T cells, and deficiency impacted at the level of apoptosis and proliferation of these cells. This led to a loss of Foxp3(+) cells over time, particularly in competitive settings, and culminated in a range of immunologic perturbations. Thus, miR-17 ∼ 92a-target interactions are part of the essential microRNA networks that safeguard the regulatory T cell lineage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Apoptosis
  • Bone Marrow Cells / cytology
  • Cell Lineage
  • Cell Proliferation
  • Female
  • Flow Cytometry
  • Forkhead Transcription Factors / metabolism*
  • Gene Regulatory Networks
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • MicroRNAs / genetics*
  • Multigene Family
  • T-Lymphocytes, Regulatory / cytology*

Substances

  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • MicroRNAs
  • Mirn17 microRNA, mouse
  • Mirn92 microRNA, mouse

Grants and funding

This work was funded by grants from the National Health and Medical Research Council, Australia (#637338 and #1004541), Juvenile Diabetes Research Foundation (5-2011-100) and the Diabetes Australia Research Trust (Y13G-CHOM). MMWC is an Australian Research Council QEII Fellow. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.