Abstract
Distinct CD4(+) T cell subsets are critical for host defense and immunoregulation. Although these subsets can act as terminally differentiated lineages, they have been increasingly noted to demonstrated plasticity. MicroRNAs are factors that control T cell stability and plasticity. Here we report that naturally occurring regulatory T cells (T(reg) cells) had high expression of the microRNA miR-10a and that miR-10a was induced by retinoic acid and transforming growth factor-β (TGF-β) in inducible T(reg) cells. By simultaneously targeting the transcriptional repressor Bcl-6 and the corepressor Ncor2, miR-10a attenuated the phenotypic conversion of inducible T(reg) cells into follicular helper T cells. We also found that miR-10a limited differentiation into the T(H)17 subset of helper T cells and therefore represents a factor that can fine-tune the plasticity and fate of helper T cells.
Publication types
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Differentiation / immunology
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Down-Regulation / immunology
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Flow Cytometry
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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MicroRNAs / biosynthesis*
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MicroRNAs / genetics
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MicroRNAs / immunology
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Nuclear Receptor Co-Repressor 2 / immunology
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Phenotype
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Proto-Oncogene Proteins c-bcl-6 / immunology
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Proto-Oncogene Proteins c-bcl-6 / metabolism*
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RNA, Messenger / biosynthesis
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RNA, Messenger / chemistry
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RNA, Messenger / genetics
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Reverse Transcriptase Polymerase Chain Reaction
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T-Box Domain Proteins / immunology
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T-Lymphocytes, Helper-Inducer / drug effects*
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T-Lymphocytes, Helper-Inducer / immunology
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T-Lymphocytes, Helper-Inducer / physiology
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T-Lymphocytes, Regulatory / drug effects*
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T-Lymphocytes, Regulatory / immunology
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T-Lymphocytes, Regulatory / physiology
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Transcription, Genetic
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Transforming Growth Factor beta / pharmacology*
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Tretinoin / pharmacology*
Substances
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MIRN10 microRNA, mouse
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MicroRNAs
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Ncor2 protein, mouse
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Nuclear Receptor Co-Repressor 2
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Proto-Oncogene Proteins c-bcl-6
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RNA, Messenger
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T-Box Domain Proteins
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T-box transcription factor TBX21
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Transforming Growth Factor beta
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Tretinoin