Activated natural killer cells (NK cells) can release NK-like cytotoxic factor (NKCF), perforin, and other pro-inflammatory cytokines, exerting cytotoxic effects. A high proportion of mesenchymal stem cells (MSCs) can inhibit NK cell proliferation, differentiation, and activation.
MSCs can inhibit NK cell proliferation, interfere with their cytotoxicity, and inhibit the secretion of pro-inflammatory cytokines. They can enhance NK cell cytotoxicity after activation by IL-2 or IL-15. When MSCs were cocultured with NK cells, IL-2/IL-15 and IFN-γ levels decreased, inhibiting NK cell growth. In addition, inhibition of NK cell cytotoxicity was associated with a decrease in activating receptors such as NKG2D, NKp30, and NKp44 by MSCs. Cytokines secreted by mesenchymal stem cells, such as PGE2, TNF-α, IDO, and HLA-G5, play key inhibitory roles.
HLA-G isoforms can be recognized by inhibitory receptors on the surface of natural killer cells, thereby inhibiting IFN-γ secretion and NK cell cytotoxicity.
Mesenchymal stem cells (MSCs) cannot be lysed by dormant natural killer cells in vivo, but activated natural killer cells can induce their own death. MSCs regulate NK cell activities by activating receptor signals rather than weakening NK cell inhibitory signals. Furthermore, after preconditioning with interferon-gamma (IFN-γ), the expression of the activating signal ULBP3 can be reduced, while the inhibitory signal of the major histocompatibility complex (MHC) class I molecule can be elevated. This protects MSCs from lysis by the mass generation of interferon-gamma (IFN-γ) and activated natural killer cells under an inflammatory environment. Therefore, pretreatment with interferon-gamma (IFN-γ) can improve the tolerance of mesenchymal stem cells to the toxic effects of natural killer cells.
