• Open Access

TLR Ligands Stimulation Protects MSC from NK Killing

Authors

  • Massimo Giuliani,

    Corresponding author
    1. Military Blood Centre (CTSA), Percy Hospital, Paris, France
    • Correspondence: Massimo Giuliani, Ph.D., Military Blood Center, Percy Hospital, Clamart, Paris, France. Telephone: 33-1-41-46-72-72; e-mail: giulianimas@hotmail.com; or Annelise Bennaceur-Griscelli, M.D., Ph.D., UMR 935 INSERM, ESTeam Paris Sud Human Embryonic Stem Cell Core Facility, APHP, Paul Brousse Hospital, Villejuif, France. e-mail: abenna@hotmail.fr

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  • Annelise Bennaceur-Griscelli,

    Corresponding author
    1. UMR 935 INSERM, ESTeam Paris Sud Human embryonic stem cell Core Facility, Paris, France
    2. APHP, Paul Brousse Hospital, France
    3. Faculty of Medicine, University of Paris 11, Paris, France
    • Correspondence: Massimo Giuliani, Ph.D., Military Blood Center, Percy Hospital, Clamart, Paris, France. Telephone: 33-1-41-46-72-72; e-mail: giulianimas@hotmail.com; or Annelise Bennaceur-Griscelli, M.D., Ph.D., UMR 935 INSERM, ESTeam Paris Sud Human Embryonic Stem Cell Core Facility, APHP, Paul Brousse Hospital, Villejuif, France. e-mail: abenna@hotmail.fr

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  • Arash Nanbakhsh,

    1. UMR 753 INSERM, Gustave Roussy Institute, Paris, France
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  • Noufissa Oudrhiri,

    1. UMR 935 INSERM, ESTeam Paris Sud Human embryonic stem cell Core Facility, Paris, France
    2. APHP, Paul Brousse Hospital, France
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  • Salem Chouaib,

    1. UMR 753 INSERM, Gustave Roussy Institute, Paris, France
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  • Bruno Azzarone,

    1. Department of Immunology, Giannina Gaslini Institute, Genoa, Italy
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  • Antoine Durrbach,

    1. Faculty of Medicine, University of Paris 11, Paris, France
    2. UMR 1014 INSERM, Hôpital Paul Brousse, Paris, France
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  • Jean-Jacques Lataillade

    1. Military Blood Centre (CTSA), Percy Hospital, Paris, France
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Abstract

Mesenchymal stem cells (MSCs) play a fundamental role in allograft rejection and graft-versus-host disease through their immunosuppressive abilities. Recently, Toll-like receptors (TLR) have been shown to modulate MSC functions. The aim of this study was to investigate the effects of several TLR ligands on the interaction between MSC and natural killer (NK) cells. Our results show that TLR-primed adult bone marrow and embryonic MSC are more resistant than unprimed MSC to IL-2-activated NK-induced killing. Such protection can be explained by the modulation of Natural Killer group 2D ligands major histocompatibility complex class I chain A and ULBP3 and DNAM-1 ligands by TLR-primed MSC. These results indicate that MSCs are able to adapt their immuno-behavior in an inflammatory context, decreasing their susceptibility to NK killing. In addition, TLR3 but not TLR4-primed MSC enhance their suppressive functions against NK cells. However, the efficiency of this response is heterogeneous, even if the phenotypes of different analyzed MSC are rather homogeneous. The consequences could be important in MSC-mediated cell therapy, since the heterogeneity of adult MSC responders may be explored in order to select the more efficient responders. Stem Cells 2014;32:290–300

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