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    MicroRNA-155 induction via TNF-α and IFN-γ suppresses expression of programmed death ligand-1 (PD-L1) in human primary cells. 
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    • MicroRNA-155 induction via TNF-α and IFN-γ suppresses expression of programmed death ligand-1 (PD-L1) in human primary cells.
    •   QMRO Home
    • Barts Cancer Institute
    • Centre for Molecular Oncology
    • MicroRNA-155 induction via TNF-α and IFN-γ suppresses expression of programmed death ligand-1 (PD-L1) in human primary cells.
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    MicroRNA-155 induction via TNF-α and IFN-γ suppresses expression of programmed death ligand-1 (PD-L1) in human primary cells.

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    Publisher version (2.968Mb)
    Volume
    292
    Pagination
    20683 - 20693
    DOI
    10.1074/jbc.M117.809053
    Journal
    J Biol Chem
    Issue
    50
    Metadata
    Show full item record
    Abstract
    Programmed death ligand-1 (PD-L1) is a critical regulator of T cell function contributing to peripheral immune tolerance. Although it has been shown that posttranscriptional regulatory mechanisms control PD-L1 expression in cancer, it remains unknown whether such regulatory loops operate also in non-transformed cells. Here we studied PD-L1 expression in human dermal lymphatic endothelial cells (HDLECs), which play key roles in immunity and cancer. Treatment of HDLECs with the pro-inflammatory cytokines IFN-γ and TNF-α synergistically up-regulated PD-L1 expression. IFN-γ and TNF-α also affected expression of several microRNAs (miRNAs) that have the potential to suppress PD-L1 expression. The most highly up-regulated miRNA following IFN-γ and TNF-α treatment in HDLECs was miR-155, which has a central role in the immune system and cancer. Induction of miR-155 was driven by TNF-α, the effect of which was significantly enhanced by IFN-γ. The PD-L1 3'-UTR contains two functional miR-155-binding sites. Endogenous miR-155 controlled the kinetics and maximal levels of PD-L1 induction upon IFN-γ and TNF-α treatments. We obtained similar findings in dermal fibroblasts, demonstrating that the IFN-γ/TNF-α/miR-155/PD-L1 pathway is not restricted to HDLECs. These results reveal miR-155 as a critical component of an inflammation-induced regulatory loop controlling PD-L1 expression in primary cells.
    Authors
    Yee, D; Shah, KM; Coles, MC; Sharp, TV; Lagos, D
    URI
    http://qmro.qmul.ac.uk/xmlui/handle/123456789/28603
    Collections
    • Centre for Molecular Oncology [260]
    Language
    eng
    Licence information
    "This research was originally published in Journal of Biological Chemistry. Yee, D., Shah, K.M., Coles, M.C., Sharp, T.V. and Lagos, D. MicroRNA-155 induction via TNF-α and IFN-γ suppresses expression of programmed death ligand-1 (PD-L1) in human primary cells. Journal of Biological Chemistry 2017; pp.jbc-M117 © the American Society for Biochemistry and Molecular Biology."
    Copyright statements
    © 2017, The American Society for Biochemistry and Molecular Biology.
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