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Updated: Apr 4, 2026

Selective Harvesting of Marginating-hepatic Leukocytes
Published on: July 21, 2016
Bone marrow-derived mesenchymal stem cells suppress NK cell recruitment and activation in PolyI:C-induced liver
Mengmeng Qu1, Jun Cui1, Jun Zhu1
1School of Basic Medical Sciences, Wuhan University, Wuhan 430071, PR China.
Abstract:
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.
Insights
Bone marrow-derived mesenchymal stem cells (BM-MSCs) reduce liver injury by suppressing natural killer (NK) cells. BM-MSCs decrease NK cell accumulation and activation, offering therapeutic potential for immune-mediated liver diseases.
Area of Science:
- Immunology
- Hepatology
- Stem Cell Biology
Background:
- Mesenchymal stem cells (MSCs) possess immunomodulatory properties with therapeutic potential for immune diseases.
- The impact of MSCs on hepatic immunity, particularly in liver injury models, remains incompletely understood.
- Natural killer (NK) cells are implicated in the pathogenesis of various liver injuries.
Purpose of the Study:
- To investigate the effect of bone marrow-derived MSCs (BM-MSCs) on hepatic NK cells in a polyinosinic-polycytidylic acid (PolyI:C)-induced liver injury model.
- To elucidate the mechanisms by which BM-MSCs modulate NK cell activity in the context of liver injury.
Main Methods:
- Induction of liver injury in mice using PolyI:C.
- Adoptive transfer of BM-MSCs into injured mice.
- Assessment of liver injury markers (ALT levels, lymphocyte infiltration).
- Analysis of NK cell accumulation, activation, and expression of sphingosine-1-phosphate receptor type 5 (S1PR5).
- In vitro co-culture of NK cells with BM-MSCs.
- Evaluation of NK cell chemotaxis towards sphingosine-1-phosphate (S1P).
Main Results:
- Adoptive transfer of BM-MSCs ameliorated PolyI:C-induced liver injury, evidenced by reduced alanine aminotransferase levels and decreased hepatic lymphocyte infiltration.
- BM-MSCs significantly suppressed NK cell accumulation and activation within the liver.
- Co-culture with BM-MSCs reduced S1PR5 expression on NK cells, impairing their trafficking.
- BM-MSC administration inhibited PolyI:C-induced S1PR5 upregulation in the liver and suppressed NK cell chemotaxis mediated by S1P.
Conclusions:
- BM-MSCs effectively mitigate liver injury induced by PolyI:C, partly through the suppression of hepatic NK cell activity.
- BM-MSCs modulate NK cell function by downregulating S1PR5 expression and inhibiting S1P-driven chemotaxis.
- These findings highlight a novel mechanism of BM-MSC immunosuppression and support their therapeutic application in immune-mediated liver disorders involving NK cells.
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