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
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Research Support, Non-U.S. Gov't
MeSH terms
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Alleles
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Animals
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Apoptosis
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Bone Marrow Cells / cytology
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Cell Lineage
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Cell Proliferation
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Female
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Flow Cytometry
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Forkhead Transcription Factors / metabolism*
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Gene Regulatory Networks
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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MicroRNAs / genetics*
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Multigene Family
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T-Lymphocytes, Regulatory / cytology*
Substances
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Forkhead Transcription Factors
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Foxp3 protein, mouse
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MicroRNAs
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Mirn17 microRNA, mouse
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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.