Mesenchymal stem cells alleviate Propionibacterium acnes-primed mice liver injury by inducing differentiation of regulatory DCs (P1098)

Abstract

Abstract Fulminant hepatic failure is a clinical syndrome characterized by sudden and severe impairment of liver function. Mesenchymal stem cells have been proposed as a promising therapeutic approach for fulminant hepatic failure. In this study, we have used Propionibacterium acnes-primed, LPS-induced liver injury in mice as an animal model of human fulminant hepatic failure. We demonstrated that administration of mesenchymal stem cells significantly ameliorated liver injury and improved the survival rates of mice subjected to fulminant hepatic failure. Therapeutic efficacy of mesenchymal stem cells could be attributed to decreased infiltration of CD4+ T cells in the liver, inhibition of Th1 cells, and induction of regulatory T cells. Intriguingly, a distinct liver population of CD11c+MHCIIhiCD80loCD86lo regulatory DCs was induced. Further mechanistic studies demonstrated that mesenchymal stem cell-derived prostaglandin E2 and one of its receptors, EP4, played essential roles in the differentiation of CD11c+B220- DC precursors into regulatory DCs in a PI3K-dependent manner. Our findings demonstrated, for the first time, critical regulatory properties of mesenchymal stem cells for induction of regulatory DCs from CD11c+B220- DC precursors. This study further lays a solid foundation for application of mesenchymal stem cells in fulminant hepatic failure therapy.