Abstract
MSCs possess potent immunosuppressive capacity. We have reported that mouse MSCs inhibit T cell proliferation and function via nitric oxide. This immune regulatory capacity of MSCs is induced by the inflammatory cytokines IFNγ together with either TNFα or IL-1β. This effect of inflammatory cytokines on MSCs is extraordinary; logarithmic increases in the expression of iNOS and chemokines are often observed. To investigate the molecular mechanisms underlying this robust effect of cytokines, we examined the expression of microRNAs in MSCs before and after cytokine treatment. We found that miR-155 is most significantly up-regulated. Furthermore, our results showed that miR-155 inhibits the immunosuppressive capacity of MSCs by reducing iNOS expression. We further demonstrated that miR-155 targets TAK1-binding protein 2 (TAB2) to regulate iNOS expression. Additionally, knockdown of TAB2 reduced iNOS expression. In summary, our study demonstrated that miR-155 inhibits the immunosuppressive capacity of MSCs by reducing iNOS expression by targeting TAB2. Our data revealed a novel role of miR-155 in regulating the immune modulatory activities of MSCs.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / immunology*
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Adaptor Proteins, Signal Transducing / metabolism
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Animals
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Cell Line
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Gene Expression Regulation, Enzymologic / genetics
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Gene Expression Regulation, Enzymologic / immunology*
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Gene Knockdown Techniques
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Humans
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Immune Tolerance / physiology*
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Interferon-gamma / genetics
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Interferon-gamma / immunology
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Interferon-gamma / metabolism
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Interleukin-1beta / genetics
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Interleukin-1beta / immunology
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Interleukin-1beta / metabolism
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Mesenchymal Stem Cells / cytology
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Mesenchymal Stem Cells / immunology*
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Mesenchymal Stem Cells / metabolism
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Mice
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MicroRNAs / genetics
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MicroRNAs / immunology*
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MicroRNAs / metabolism
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Nitric Oxide Synthase Type II / biosynthesis
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Nitric Oxide Synthase Type II / genetics
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Nitric Oxide Synthase Type II / immunology*
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / immunology
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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Interleukin-1beta
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MicroRNAs
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Mirn155 microRNA, mouse
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Tab2 protein, mouse
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Tumor Necrosis Factor-alpha
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Interferon-gamma
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Nitric Oxide Synthase Type II
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Nos2 protein, mouse