Fig. 2

Intercellular communication and potential outcomes between NK cells and MSCs. During the stage phase, MSCs upregulate the cytotoxic capabilities of NK cells. NK-MSC interactions lead to the secretion of IFN-γ by NK cells. Activated MSCs with IFN-γ (MSC1) increase their levels of MHC class I. Boosting MHC class I presentation may provide MSCs with protection against the destruction caused by NK cells [230, 231]. This is accomplished by shifting the balance towards the inhibition of NK cell activity, which results in the transmission of inhibitory signals and the hindrance of the cytotoxic capabilities of NK cells [232]. Nevertheless, there is evidence indicating that MSCs could be regarded as targets sensitive to lysis by activated NK cells [128, 218, 233]. On the contrary, during the resolution phase of inflammation, MSCs in a bioactive mediators-dependent manner induce an inhibitory effect on NK cell proliferation, cytokine secretion, expression of surface-activating receptors, and coreceptors, as well as induce senescence of inflammatory NK cells with a less responsive phenotype [55, 208]. IDO, PGE2, TGF-β, IL-10, and sHLA-G5 are key regulators of the mentioned effects. Furthermore, scientific evidence has demonstrated that MSCs exhibit the capacity to directly hinder the cytotoxic capability of NK cells through the downregulation of perforin and STAT3 [218, 234]. Overall, MSCs have the capability to enhance the cytotoxic activity of NK cells during the initial stages. Subsequently, they have the potential to promote a regulatory phenotype or trigger senescence in activated NK cells [208]. Importantly, it has also been postulated that MSCs exhibit inherent heterogeneity, which may influence the MSC-NK cell interaction [235]. Additionally, MSCs demonstrate varied crosstalk patterns with different NK cell populations [236]