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Stem Cells Dev. 2018 Oct 17. doi: 10.1089/scd.2018.0015. [Epub ahead of print]

Human Fetal Liver Mesenchymal Stem Cell derived Exosomes impair NK cell function.

Author information

1
INSERM UMRS-MD 1197, Villejuif, idf, France ; fanye39@hotmail.com.
2
INSERM UMRS-MD 1197, Villejuif, idf, France ; herr.florence@gmail.com.
3
INSERM UMRS-MD 1197, Villejuif, idf, France ; vernocheta@gmail.com.
4
hopital Pontoise, gynecologie, pontoise, France ; benoit.mennesson@ch-pontoise.fr.
5
INSERM UMRS-MD 1197, Villejuif, idf, France ; estelle.oberlin@inserm.fr.
6
Assistance Publique - Hopitaux de Paris, 26930, Nephrology, Le Kremlin Bicetre, Île-de-France, France.
7
INSERM UMRS-MD 1197, Villejuif, idf, France ; antoine.durrbach@inserm.fr.

Abstract

Mesenchymal stem cells (MSCs) are powerful immunomodulators that regulate the diverse functions of immune cells involved in allogeneic reactions, such as T cells and natural killer cells (NK), through cell-cell contact or secreted factors. Exosomes secreted by MSCs may be involved in their regulatory functions, providing new therapeutic tools. Here, we showed that fetal liver (FL) MSC-derived exosomes inhibit proliferation, activation, and cytotoxicity of NK cells. Exosomes bearing LAP, TGFβ, and TSP1, a regulatory molecule for TGFβ, induced downstream TGFβ/Smad2/3 signaling in NK cells. The inhibition of TGFβ using a neutralizing anti-TGFβ antibody, restored NK proliferation, differentiation, and cytotoxicity, demonstrating that FL-MSC-derived exosomes exert their inhibition on NK cell function via TGFβ. These results suggest that FL-MSC-derived exosomes regulate NK cell functions through exosome associated TGFβ.

PMID:
30328799
DOI:
10.1089/scd.2018.0015

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