Bone Marrow-derived Mesenchymal Stem Cells Suppress NK Cell Recruitment and Activation in PolyI:C-induced Liver Injury

Mesenchymal stem cells (MSCs) have been shown to have an immunomodulatory capability and clinical potential in immune diseases. However, it is unknown how MSCs may affect immunity in liver injury. This study was designed to explore the effect of bone marrow-derived MSCs (BM-MSCs) on hepatic natural killer (NK) cells in polyinosinic-polycytidylic acid (PolyI:C)-induced liver injury. Unlike in controls, adoptive transfer of BM-MSCs in mice ameliorated PolyI:C-induced liver injury, as shown by lower alanine aminotransferase levels and decreased lymphocyte infiltration in the liver. Importantly, BM-MSCs suppress NK cell accumulation and activation in the liver, which plays an important role in PolyI:C-induced liver injury. Furthermore, NK cells co-cultured with BM-MSCs reduced expression of sphingosine-1-phosphate receptor type 5 (S1PR5), an important receptor required for NK cell trafficking in vivo. BM-MSC administration suppressed the elevation of expression of S1PR5 in the liver induced by PolyI:C injection. Accordingly, BM-MSCs inhibited the chemotactic activity of NK cells induced by sphingosine-1-phosphate (S1P, the ligand of S1PR5). Our results provide an additional mechanism for the immunosuppressive effect of BM-MSCs on NK cells, which further supports the therapeutic potential of BM-MSCs in immune-mediated disorders, including those in which NK cells play a major role.