TLR Ligands Stimulation Protects MSC from NK Killing

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 lig...

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Published in:Stem cells (Dayton, Ohio) Ohio), 2014-01, Vol.32 (1), p.290-300
Main Authors: Giuliani, Massimo, Bennaceur‐Griscelli, Annelise, Nanbakhsh, Arash, Oudrhiri, Noufissa, Chouaib, Salem, Azzarone, Bruno, Durrbach, Antoine, Lataillade, Jean‐Jacques
Format: Article
Language:English
Subjects:
Bone marrow
Flow Cytometry
HeLa Cells
Humans
Immune system
Immunology
Immunotolerance
K562 Cells
Killer Cells, Natural - cytology
Killer Cells, Natural - immunology
Ligands
Mesenchymal stem cells
Mesenchymal Stromal Cells - cytology
Mesenchymal Stromal Cells - drug effects
Mesenchymal Stromal Cells - immunology
NK cells
NKG2D ligands
Stem cells
TLR
Toll-Like Receptors - metabolism
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Summary: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
ISSN:1066-5099
1549-4918
DOI:10.1002/stem.1563