Immunomodulatory effects of placenta-derived mesenchymal stem cells on T cells by regulation of FoxP3 expression

Soo Hwan Kim, Jieun Jung, Kyung Jin Cho, Jong Ho Choi, Hyeong Seon Lee, Gi Jin Kim, Seung Gwan Lee

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    19 Citations (Scopus)

    Abstract

    The immunomodulatory effects of mesenchymal stem cells (MSCs) are an important mediator of their therapeutic effects in stem cell therapy and regenerative medicine. The regulation mechanism of MSCs is orchestrated by several factors in both intrinsic and extrinsic events. Recent studies have shown that the dynamic expression of cytokines secreted from MSCs control T cell function and maturation by regulating the expression of FoxP3, which figures prominently in T cell differentiation. However, there is no evidence that placenta-derived mesenchymal stem cells (PD-MSCs) have strong immunomodulatory effects on T cell function and maturation via FoxP3 expression. Therefore, we compared the expression of FoxP3 in activated T cells isolated from peripheral blood and co-cultured with PD-MSCs or bone marrow-derived mesenchymal stem cells (BM-MSCs) and analyzed their effect on T cell proliferation and cytokine profiles. Additionally, we verified the immunomodulatory function of PD-MSCs by siRNA-mediated silencing of FoxP3. MSCs, including PD-MSCs and BM-MSCs, promoted differentiation of naive peripheral blood T cells into CD4+CD25+FoxP3+ regulatory T (Treg) cells. Intriguingly, the population of CD4+CD25+FoxP3+ Treg cells co-cultured with PD-MSCs was significantly expanded in comparison to those co-cultured with BM-MSCs or WI38 cells (p < 0.05, p < 0.001). Dynamic expression patterns of several cytokines, including anti- and pro-inflammatory cytokines and members of the transforming growth factor-beta (TGF-β) family secreted from PD-MSCs according to FoxP3 expression were observed. The results suggest that PD-MSCs have an immunomodulatory effect on T cells by regulating FoxP3 expression.

    Original languageEnglish
    Pages (from-to)196-204
    Number of pages9
    JournalInternational Journal of Stem Cells
    Volume11
    Issue number2
    DOIs
    Publication statusPublished - 2018 Nov 1

    Bibliographical note

    Funding Information:
    This work was supported by the Korea Healthcare Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number : HI16C1559).

    Publisher Copyright:
    © 2018 by the Korean Society for Stem Cell Research.

    Keywords

    • Cytokines
    • FoxP3
    • Immunomodulatory effects
    • Placenta-derived mesenchymal stem cells
    • Regulatory T cell

    ASJC Scopus subject areas

    • Developmental Biology
    • Cell Biology

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