Surface expression of HLA-G is involved in mediating immunomodulatory effects of placenta-derived multipotent cells (PDMCs) towards natural killer lymphocytes

Ko Jiunn Liu, Chia Jen Wang, Chan Jung Chang, Hsin I. Hu, Pei Ju Hsu, Yu Chen Wu, Chyi Huey Bai, Huey Kang Sytwu, B. Linju Yen

研究成果: 雜誌貢獻文章

27 引文 (Scopus)

摘要

Interactions between maternal natural killer lymphocytes (NKs) and fetal tissues are important in mediating maternal-fetal tolerance. We therefore investigated the interactions of NKs to placenta-derived multipotent cells (PDMCs) isolated from the term human placenta. PDMCs have similar cell surface marker expression as bone marrow mesenchymal stem cells (BMMSCs) and additionally express human embryonic stem cell markers SSEA-4 and CD-9. Differentiation into the tri-mesodermal lineages of osteoblastic, adipocytic, and chondrogenic phenotypes can be readily achieved under the appropriate conditions. We found that PDMCs are more resistant to NK-mediated lysis than the major histocompatibility complex (MHC) class-I null target cell K562, and can suppress NK secretion of interferon-γ (IFN-γ). Moreover, as third-party cells, PDMCs suppressed the cytotoxic effects of cytokine-stimulated NKs on K562. Pretreatment of PDMCs with IFN-γ, a proinflammatory cytokine, surprisingly enhanced such immunosuppressive effects. Cell-cell contact between NKs and PDMCs is required for suppressive effects, which are partially mediated by slight upregulation of the NK inhibitory receptor killer inhibitory receptor and downregulation of the activating receptor NKp30. Moreover, enhancement of PDMC suppressive effects is also mediated by IFN-γ-induced surface expression of HLA-G-an immunomodulatory nonclassical MHC class I molecule-on PDMCs, as seen by partial reversibility with HLA-G neutralizing antibodies. With its broad immunosuppressive properties, PDMCs may represent a potential cell source for therapeutic use

原文英語
頁(從 - 到)1721-1730
頁數10
期刊Cell Transplantation
20
發行號11-12
DOIs
出版狀態已發佈 - 2011

指紋

HLA-G Antigens
Interferons
Lymphocytes
Natural Killer Cells
Placenta
Stem cells
Antibodies
Bone
Tissue
Molecules
Immunosuppressive Agents
Major Histocompatibility Complex
Natural Cytotoxicity Triggering Receptor 3
Mothers
KIR Receptors
Cytokines
Null Lymphocytes
Therapeutic Uses

ASJC Scopus subject areas

  • Cell Biology
  • Transplantation
  • Biomedical Engineering

引用此文

Surface expression of HLA-G is involved in mediating immunomodulatory effects of placenta-derived multipotent cells (PDMCs) towards natural killer lymphocytes. / Liu, Ko Jiunn; Wang, Chia Jen; Chang, Chan Jung; Hu, Hsin I.; Hsu, Pei Ju; Wu, Yu Chen; Bai, Chyi Huey; Sytwu, Huey Kang; Linju Yen, B.

於: Cell Transplantation, 卷 20, 編號 11-12, 2011, p. 1721-1730.

研究成果: 雜誌貢獻文章

Liu, Ko Jiunn ; Wang, Chia Jen ; Chang, Chan Jung ; Hu, Hsin I. ; Hsu, Pei Ju ; Wu, Yu Chen ; Bai, Chyi Huey ; Sytwu, Huey Kang ; Linju Yen, B. / Surface expression of HLA-G is involved in mediating immunomodulatory effects of placenta-derived multipotent cells (PDMCs) towards natural killer lymphocytes. 於: Cell Transplantation. 2011 ; 卷 20, 編號 11-12. 頁 1721-1730.
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abstract = "Interactions between maternal natural killer lymphocytes (NKs) and fetal tissues are important in mediating maternal-fetal tolerance. We therefore investigated the interactions of NKs to placenta-derived multipotent cells (PDMCs) isolated from the term human placenta. PDMCs have similar cell surface marker expression as bone marrow mesenchymal stem cells (BMMSCs) and additionally express human embryonic stem cell markers SSEA-4 and CD-9. Differentiation into the tri-mesodermal lineages of osteoblastic, adipocytic, and chondrogenic phenotypes can be readily achieved under the appropriate conditions. We found that PDMCs are more resistant to NK-mediated lysis than the major histocompatibility complex (MHC) class-I null target cell K562, and can suppress NK secretion of interferon-γ (IFN-γ). Moreover, as third-party cells, PDMCs suppressed the cytotoxic effects of cytokine-stimulated NKs on K562. Pretreatment of PDMCs with IFN-γ, a proinflammatory cytokine, surprisingly enhanced such immunosuppressive effects. Cell-cell contact between NKs and PDMCs is required for suppressive effects, which are partially mediated by slight upregulation of the NK inhibitory receptor killer inhibitory receptor and downregulation of the activating receptor NKp30. Moreover, enhancement of PDMC suppressive effects is also mediated by IFN-γ-induced surface expression of HLA-G-an immunomodulatory nonclassical MHC class I molecule-on PDMCs, as seen by partial reversibility with HLA-G neutralizing antibodies. With its broad immunosuppressive properties, PDMCs may represent a potential cell source for therapeutic use",
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AU - Liu, Ko Jiunn

AU - Wang, Chia Jen

AU - Chang, Chan Jung

AU - Hu, Hsin I.

AU - Hsu, Pei Ju

AU - Wu, Yu Chen

AU - Bai, Chyi Huey

AU - Sytwu, Huey Kang

AU - Linju Yen, B.

PY - 2011

Y1 - 2011

N2 - Interactions between maternal natural killer lymphocytes (NKs) and fetal tissues are important in mediating maternal-fetal tolerance. We therefore investigated the interactions of NKs to placenta-derived multipotent cells (PDMCs) isolated from the term human placenta. PDMCs have similar cell surface marker expression as bone marrow mesenchymal stem cells (BMMSCs) and additionally express human embryonic stem cell markers SSEA-4 and CD-9. Differentiation into the tri-mesodermal lineages of osteoblastic, adipocytic, and chondrogenic phenotypes can be readily achieved under the appropriate conditions. We found that PDMCs are more resistant to NK-mediated lysis than the major histocompatibility complex (MHC) class-I null target cell K562, and can suppress NK secretion of interferon-γ (IFN-γ). Moreover, as third-party cells, PDMCs suppressed the cytotoxic effects of cytokine-stimulated NKs on K562. Pretreatment of PDMCs with IFN-γ, a proinflammatory cytokine, surprisingly enhanced such immunosuppressive effects. Cell-cell contact between NKs and PDMCs is required for suppressive effects, which are partially mediated by slight upregulation of the NK inhibitory receptor killer inhibitory receptor and downregulation of the activating receptor NKp30. Moreover, enhancement of PDMC suppressive effects is also mediated by IFN-γ-induced surface expression of HLA-G-an immunomodulatory nonclassical MHC class I molecule-on PDMCs, as seen by partial reversibility with HLA-G neutralizing antibodies. With its broad immunosuppressive properties, PDMCs may represent a potential cell source for therapeutic use

AB - Interactions between maternal natural killer lymphocytes (NKs) and fetal tissues are important in mediating maternal-fetal tolerance. We therefore investigated the interactions of NKs to placenta-derived multipotent cells (PDMCs) isolated from the term human placenta. PDMCs have similar cell surface marker expression as bone marrow mesenchymal stem cells (BMMSCs) and additionally express human embryonic stem cell markers SSEA-4 and CD-9. Differentiation into the tri-mesodermal lineages of osteoblastic, adipocytic, and chondrogenic phenotypes can be readily achieved under the appropriate conditions. We found that PDMCs are more resistant to NK-mediated lysis than the major histocompatibility complex (MHC) class-I null target cell K562, and can suppress NK secretion of interferon-γ (IFN-γ). Moreover, as third-party cells, PDMCs suppressed the cytotoxic effects of cytokine-stimulated NKs on K562. Pretreatment of PDMCs with IFN-γ, a proinflammatory cytokine, surprisingly enhanced such immunosuppressive effects. Cell-cell contact between NKs and PDMCs is required for suppressive effects, which are partially mediated by slight upregulation of the NK inhibitory receptor killer inhibitory receptor and downregulation of the activating receptor NKp30. Moreover, enhancement of PDMC suppressive effects is also mediated by IFN-γ-induced surface expression of HLA-G-an immunomodulatory nonclassical MHC class I molecule-on PDMCs, as seen by partial reversibility with HLA-G neutralizing antibodies. With its broad immunosuppressive properties, PDMCs may represent a potential cell source for therapeutic use

KW - HLA-G

KW - Immunomodulation

KW - Mesenchymal stem cells (MSCs)

KW - Natural killer lymphocytes

KW - Placenta

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