dc.contributor.author | Yee, D | en_US |
dc.contributor.author | Shah, KM | en_US |
dc.contributor.author | Coles, MC | en_US |
dc.contributor.author | Sharp, TV | en_US |
dc.contributor.author | Lagos, D | en_US |
dc.date.accessioned | 2017-11-03T16:33:27Z | |
dc.date.available | 2017-08-01 | en_US |
dc.date.issued | 2017-12-15 | en_US |
dc.date.submitted | 2017-11-03T10:04:57.854Z | |
dc.identifier.uri | http://qmro.qmul.ac.uk/xmlui/handle/123456789/28603 | |
dc.description.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. | en_US |
dc.description.sponsorship | DY is supported by the BBSRC Doctoral Training Program in “Mechanistic Biology and its Strategic
Application” (BB/J01113/1). Additional funding was provided by grants awarded to DL (MRC New
Investigator Research Grant MR/L008505/1), and TVS (BBSRC, BB/I007571/2). We thank the
Genomics Lab at the University of York Biology Technology Facility for small RNA sequencing. We
thank Dr Rinako Nakagawa for 3’-UTR PU.1 psiCheck2 constructs. | en_US |
dc.format.extent | 20683 - 20693 | en_US |
dc.language | eng | en_US |
dc.relation.ispartof | J Biol Chem | en_US |
dc.rights | "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." | |
dc.subject | PD-L1 | en_US |
dc.subject | endothelial cell | en_US |
dc.subject | fibroblast | en_US |
dc.subject | immune checkpoint inhibitors | en_US |
dc.subject | inflammation | en_US |
dc.subject | interferon | en_US |
dc.subject | lymphatic endothelial cells | en_US |
dc.subject | miR-155 | en_US |
dc.subject | microRNA (miRNA) | en_US |
dc.subject | 3' Untranslated Regions | en_US |
dc.subject | B7-H1 Antigen | en_US |
dc.subject | Base Sequence | en_US |
dc.subject | Binding Sites | en_US |
dc.subject | Cells, Cultured | en_US |
dc.subject | Dermis | en_US |
dc.subject | Endothelium, Lymphatic | en_US |
dc.subject | Gene Expression Profiling | en_US |
dc.subject | Gene Expression Regulation | en_US |
dc.subject | Genes, Reporter | en_US |
dc.subject | Humans | en_US |
dc.subject | Interferon-gamma | en_US |
dc.subject | Kinetics | en_US |
dc.subject | MicroRNAs | en_US |
dc.subject | Microscopy, Fluorescence | en_US |
dc.subject | RNA Interference | en_US |
dc.subject | RNA, Small Interfering | en_US |
dc.subject | Recombinant Proteins | en_US |
dc.subject | Response Elements | en_US |
dc.subject | Tumor Necrosis Factor-alpha | en_US |
dc.title | MicroRNA-155 induction via TNF-α and IFN-γ suppresses expression of programmed death ligand-1 (PD-L1) in human primary cells. | en_US |
dc.type | Article | |
dc.rights.holder | © 2017, The American Society for Biochemistry and Molecular Biology. | |
dc.identifier.doi | 10.1074/jbc.M117.809053 | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/29066622 | en_US |
pubs.issue | 50 | en_US |
pubs.notes | No embargo | en_US |
pubs.publication-status | Published | en_US |
pubs.volume | 292 | en_US |