期刊
JOURNAL OF CELLULAR PHYSIOLOGY
卷 233, 期 7, 页码 5243-5254出版社
WILEY
DOI: 10.1002/jcp.26305
关键词
FSK-MSCs; immunomodulation; NK cells
资金
- Le Fonds National de la Recherche Scientifique, F.R.S.-FNRS
- Televie
Foreskin-mesenchymal stromal cells (FSK-MSCs) are immune-privileged thus making them valuable immunotherapeutic cell product. Characterization of the relationship between FSK-MSCs and natural killer (NK) cells is essential to improve cell-based therapy. In the present study, we studied for the first time FSK-MSCs-NK interaction and showed that the result of such cross talk was robustly dependent on the type of cytokines (IL-2, IL-12, IL-15, and IL-21) employed to activate NK cells. Distinctly activated-NK cells showed uneven cytotoxicity against FSK-MSCs, triggering their death in fine. The expression of different cell-surface ligands (CD112, CD155, ULPB-3) and receptors (LAIR, KIRs) ensuring such interaction was altered following co-culture of both populations. Despite their partial negative effect on NK cell proliferation, FSK-MSCs boosted the capacity of activated NK-cells to secrete IFN- and TNF-. Moreover, FSK-MSCs enhanced degranulation of NK cells, reinforced secretion of perforin and granzymes, while only modestly increased ROS production. On the other hand, FSK-MSCs-mediated expression of C1 and B9 serpins was significantly lowered in the presence of activated NK cells. Altogether, our results highlight major immunological changes following FSK-MSCs-NK interaction. Understanding these outcomes will therefore enhance the value of the therapeutic strategy.
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