B7-H1-mediated immunosuppressive properties in human mesenchymal stem cells are mediated by STAT-1 and not PI3K/Akt signaling

In Keun Jang, Hyun Joo Jung, O. Kyu Noh, Doo Hoon Lee, Kwang Chul Lee, Jun Eun Park

    Research output: Contribution to journalArticlepeer-review

    2 Citations (Scopus)

    Abstract

    Mesenchymal stem cells (MSCs), derived from either bone marrow (BM) or Wharton's jelly (WJ), inhibit the proliferation of activated T cells, and interferon (IFN)-? serves an important role in this process. This process is B7-homolog (H)1-dependent during cell contact inhibition. However, the signaling pathway involved in B7-H1 expression in MSCs remains largely undefined. The present study demonstrated activation of B7-H1 by engaging signal transducer and activator of transcription (STAT)-1 signaling in MSCs. Human BM- and WJ-MSCs were isolated and cultured. The immunosuppressive effect of BM- and WJ-MSCs on phytohemagglutinin (PHA)-induced T cell proliferation was compared using direct and indirect co-culture systems. B7-H1 expression on BM- and WJ-MSCs was detected by flow cytometry. Small interfering (si)RNA was used to knock down the expression of STAT-1. The inhibitory effect of MSCs on T lymphocytes was observed using PHA-induced T cell proliferation assays. IFN-?-induced B7-H1 expression on human BM- and WJ-MSCs increased in a time-dependent manner. Furthermore, the inhibitory effect of MSCs on T cell proliferation was be restored when an anti-B7-H1 monoclonal antibody was used. When STAT-1 signaling was inhibited by siRNA, B7-H1 expression on IFN-?-treated MSCs decreased and T cell proliferation was restored; however, the expression of B7-H1 did not alter upon treatment with a phosphatidylinositol-3-kinase (PI3K) inhibitor (LY294002). These results demonstrated that the IFN-?-induced immunosuppressive properties of B7-H1 in human BM- and WJ-MSCs were mediated by STAT-1 signaling, and not by PI3K/RAC-a serine/threonine-protein kinase signaling. Understanding the intracellular mechanisms underlying IFN-?-induced expression of B7-H1 in MSCs may ultimately lead to an improved understanding of MSCs and provide insight into their use as cell therapy agents.

    Original languageEnglish
    Pages (from-to)1842-1848
    Number of pages7
    JournalMolecular Medicine Reports
    Volume18
    Issue number2
    DOIs
    Publication statusPublished - 2018 Aug

    Keywords

    • Activator of transcription 1
    • B7-homolog 1
    • Interferon-?
    • Mesenchymal stem cells
    • Phosphatidylinositol-3-kinase/RAC-a serine/threonine-protein kinase
    • Signal transducer

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Medicine
    • Molecular Biology
    • Genetics
    • Oncology
    • Cancer Research

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