Abstract
We found upregulation of expression of the microRNA miR-155 in primary effector and effector memory CD8(+) T cells, but low miR-155 expression in naive and central memory cells. Antiviral CD8(+) T cell responses and viral clearance were impaired in miR-155-deficient mice, and this defect was intrinsic to CD8(+) T cells, as miR-155-deficient CD8(+) T cells mounted greatly diminished primary and memory responses. Conversely, miR-155 overexpression augmented antiviral CD8(+) T cell responses in vivo. Gene-expression profiling showed that miR-155-deficient CD8(+) T cells had enhanced type I interferon signaling and were more susceptible to interferon's antiproliferative effect. Inhibition of the type I interferon-associated transcription factors STAT1 or IRF7 resulted in enhanced responses of miR-155-deficient CD8(+) T cells in vivo. We have thus identified a previously unknown role for miR-155 in regulating responsiveness to interferon and CD8(+) T cell responses to pathogens in vivo.
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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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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Cell Proliferation / drug effects
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Flow Cytometry
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Gene Expression Profiling
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Gene Regulatory Networks / genetics
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Gene Regulatory Networks / immunology
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Immunoblotting
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Immunologic Memory / genetics
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Immunologic Memory / immunology
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Interferon Regulatory Factor-7 / genetics
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Interferon Regulatory Factor-7 / immunology
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Interferon Regulatory Factor-7 / metabolism
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Interferons / immunology*
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Interferons / metabolism
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Interferons / pharmacology
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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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MicroRNAs / immunology*
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MicroRNAs / metabolism
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Oligonucleotide Array Sequence Analysis
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Orthomyxoviridae / immunology
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Orthomyxoviridae Infections / genetics
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Orthomyxoviridae Infections / immunology
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Orthomyxoviridae Infections / virology
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RNA Interference
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Reverse Transcriptase Polymerase Chain Reaction
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STAT1 Transcription Factor / genetics
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STAT1 Transcription Factor / immunology
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STAT1 Transcription Factor / metabolism
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Signal Transduction / genetics
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Signal Transduction / immunology*
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Suppressor of Cytokine Signaling 1 Protein
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Suppressor of Cytokine Signaling Proteins / genetics
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Suppressor of Cytokine Signaling Proteins / immunology
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Suppressor of Cytokine Signaling Proteins / metabolism
Substances
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Interferon Regulatory Factor-7
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Irf7 protein, mouse
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MicroRNAs
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Mirn155 microRNA, mouse
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STAT1 Transcription Factor
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Socs1 protein, mouse
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Suppressor of Cytokine Signaling 1 Protein
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Suppressor of Cytokine Signaling Proteins
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Interferons