L'effet immunomodulateur de cellule souche mésenchymateuse et ses exosomes sur l'activité des lymphocytes

Abstract : Introduction: Mesenchymal stem cells (MSCs) are powerful immunomodulators regulating the function of B and T lymphocytes and natural killers cells (NK) involved in allogeneic reactions. Their immunomodulatory properties depend on cell contact and secretion factors produced by MSCs. Thus exosomes produced by these cells could provide new therapeutic tools.Objective: The objective of this work is to study the effect of MSC derived exosomes in vitro on B and T lymphocytes and NK cells.Method: MSCs used for this study are isolated from human fetal liver. Exosomes were isolated from MSC culture medium by a serie of ultracentrifugation at 100000g.Results: MSCs inhibit the proliferation of T lymphocytes. Unlike MSCs, their exosomes do not abrogate the proliferation of T and B cells. However they inhibit the proliferation, activation and cytotoxicity (CD107a expression) of NK cells. By FACS analysis we showed a surface expression of TGFb; by exosomes. Inhibition of NK cells activation by exosomes is altered by a neutralizing anti-TGFb; antibody. Contrary when NK cells are cultured with TGFb; the same effect qs exosomes is demonstrated. By IF, we found a nuclear translocation of Smad 2/3 (TGFb; signal transducer) in NK cells cultured with exosomes, which is inhibited by the qddition of anti-TGFb; antibody.Conclusion: These results suggest that the immunomodulatory properties of MSCs on NK could depend on exosome presentation or association with TGFb;.
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Ye Fan. L'effet immunomodulateur de cellule souche mésenchymateuse et ses exosomes sur l'activité des lymphocytes. Immunologie. Université Paris-Saclay, 2017. Français. ⟨NNT : 2017SACLS194⟩. ⟨tel-02275798⟩

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