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

  • Authors:
    • In Keun Jang
    • Hyun Joo Jung
    • O Kyu Noh
    • Doo‑Hoon Lee
    • Kwang Chul Lee
    • Jun Eun Park
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  • Published online on: May 30, 2018     https://doi.org/10.3892/mmr.2018.9102
  • Pages: 1842-1848
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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)‑γ 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‑γ‑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‑γ‑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‑γ‑induced immunosuppressive properties of B7‑H1 in human BM‑ and WJ‑MSCs were mediated by STAT‑1 signaling, and not by PI3K/RAC‑α serine/threonine‑protein kinase signaling. Understanding the intracellular mechanisms underlying IFN‑γ‑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.
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August-2018
Volume 18 Issue 2

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Jang IK, Jung HJ, Noh OK, Lee DH, Lee KC and Park JE: B7‑H1‑mediated immunosuppressive properties in human mesenchymal stem cells are mediated by STAT‑1 and not PI3K/Akt signaling. Mol Med Rep 18: 1842-1848, 2018
APA
Jang, I.K., Jung, H.J., Noh, O.K., Lee, D., Lee, K.C., & Park, J.E. (2018). B7‑H1‑mediated immunosuppressive properties in human mesenchymal stem cells are mediated by STAT‑1 and not PI3K/Akt signaling. Molecular Medicine Reports, 18, 1842-1848. https://doi.org/10.3892/mmr.2018.9102
MLA
Jang, I. K., Jung, H. J., Noh, O. K., Lee, D., Lee, K. C., Park, J. E."B7‑H1‑mediated immunosuppressive properties in human mesenchymal stem cells are mediated by STAT‑1 and not PI3K/Akt signaling". Molecular Medicine Reports 18.2 (2018): 1842-1848.
Chicago
Jang, I. K., Jung, H. J., Noh, O. K., Lee, D., Lee, K. C., Park, J. E."B7‑H1‑mediated immunosuppressive properties in human mesenchymal stem cells are mediated by STAT‑1 and not PI3K/Akt signaling". Molecular Medicine Reports 18, no. 2 (2018): 1842-1848. https://doi.org/10.3892/mmr.2018.9102