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.

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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