Mesenchymal stem cells and natural killer cells interaction mechanisms and potential clinical applications

Abstract

Natural killer cells (NK cells) are innate immune cells that are activated to fight tumor cells and virus-infected cells. NK cells also play an important role in the graft versus leukemia response. However, they can over-develop inflammatory reactions by secreting inflammatory cytokines and increasing Th1 differentiation, eventually leading to tissue damage. Today, researchers have attributed some autoimmune diseases and GVHD to NK cells. On the other hand, it has been shown that mesenchymal stem cells (MSCs) can modulate the activity of NK cells, while some researchers have shown that NK cells can cause MSCs to lysis. Therefore, we considered it is necessary to investigate the effect of these two cells and their signaling pathway in contact with each other, also their clinical applications.

Keywords: Immunomodulation; Mesenchymal stem cells; Natural killer cell; Signaling; Therapeutic.

Fig. 1

Mechanism of cell-to-cell contact between MSC and NK cells. IL-15-, IL-2-, IL-21-stimulated NK cells release inflammatory cytokines. These inflammatory cytokines affect the MSC and caused the release of PGE2 and kynurenine and other factors from the MSC. The MSC inhibits the function of NK cells by these factors. PGE2 prostaglandin E2, IL-15 interleukin-15, IL-2 interleukin-2, IL-21 interleukin-21, COX-2 cyclooxygenase-2, IDO indoleamine-2,3-dioxygenase, AA acid arachidonic, PG-H2 prostaglandin H2, IL-1β interleukin-1β, IFN-γ Interferon gamma, TNF-α Tumour Necrosis Factor alpha, EP2/3 Prostaglandin receptor, FOXO3A/CDKN1B quiescence-associated genes, IL-10 interleukin-10, HLA-G5 Human leukocyte antigen-G5, TGF-β Transforming growth factor beta, STAT4 signal transducer and activator of transcription, JAK Janus kinase, NK cell natural killer cell