TLR ligands stimulation protects MSC from NK killing

Massimo Giuliani, Annelise Bennaceur-Griscelli, Arash Nanbakhsh, Noufissa Oudrhiri, Salem Chouaib, Bruno Azzarone, Antoine Durrbach, Jean Jacques Lataillade

Research output: Contribution to journalArticle


Mesenchymal stem cells (MSCs) play a fundamental role in allograft rejection and graft-versushost 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.

Original languageEnglish
Pages (from-to)290-300
Number of pages11
JournalStem Cells
Issue number1
Publication statusPublished - Jan 2014


  • Immunotolerance
  • Mesenchymal stem cells
  • NK cells
  • NKG2D ligands
  • TLR

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine

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    Giuliani, M., Bennaceur-Griscelli, A., Nanbakhsh, A., Oudrhiri, N., Chouaib, S., Azzarone, B., Durrbach, A., & Lataillade, J. J. (2014). TLR ligands stimulation protects MSC from NK killing. Stem Cells, 32(1), 290-300.