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 journalArticle

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 1

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Phosphatidylinositol 3-Kinase
STAT1 Transcription Factor
Immunosuppressive Agents
Stem cells
Mesenchymal Stromal Cells
Wharton Jelly
T-cells
Bone
Interferons
Bone Marrow
Cell proliferation
T-Lymphocytes
Cell Proliferation
Phytohemagglutinins
Small Interfering RNA
Contact Inhibition
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Flow cytometry
Protein-Serine-Threonine Kinases
Cell- and Tissue-Based Therapy

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

Cite this

B7-H1-mediated immunosuppressive properties in human mesenchymal stem cells are mediated by STAT-1 and not PI3K/Akt signaling. / Jang, In Keun; Jung, Hyun Joo; Noh, O. Kyu; Lee, Doo Hoon; Lee, Kwang Chul; Park, Jun Eun.

In: Molecular Medicine Reports, Vol. 18, No. 2, 01.08.2018, p. 1842-1848.

Research output: Contribution to journalArticle

Jang, In Keun ; Jung, Hyun Joo ; Noh, O. Kyu ; Lee, Doo Hoon ; Lee, Kwang Chul ; Park, Jun Eun. / B7-H1-mediated immunosuppressive properties in human mesenchymal stem cells are mediated by STAT-1 and not PI3K/Akt signaling. In: Molecular Medicine Reports. 2018 ; Vol. 18, No. 2. pp. 1842-1848.
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