Yee, Daniel, Shah, Kunal M, Coles, Mark C orcid.org/0000-0001-8079-9358 et al. (2 more authors) (2017) MicroRNA-155 induction via TNF-α and IFN-γ suppresses expression of programmed death ligand-1 (PD-L1) in human primary cells. The Journal of biological chemistry. pp. 1-19. ISSN 1083-351X
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 upregulated PDL1 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 upregulated 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 treatment. 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 inflammationinduced regulatory loop controlling PD-L1 expression in primary cells.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017, The American Society for Biochemistry and Molecular Biology.Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details. |
Keywords: | Journal Article |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) The University of York > Faculty of Sciences (York) > Chemistry (York) The University of York > Faculty of Sciences (York) > Hull York Medical School (York) |
Depositing User: | Pure (York) |
Date Deposited: | 09 Nov 2017 14:19 |
Last Modified: | 22 Jan 2025 00:08 |
Published Version: | https://doi.org/10.1074/jbc.M117.809053 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1074/jbc.M117.809053 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:123811 |
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Description: J. Biol. Chem.-2017-Yee-jbc.M117.809053