Mesenchymal stem cells alleviate bacteria-induced liver injury in mice by inducing regulatory dendritic cells

Yi Zhang, Wei Cai, Qingrong Huang, Yuting Gu, Yufang Shi, Jiefang Huang, Fang Zhao, Qiang Liu, Xunbin Wei, Min Jin, Changping Wu, Qing Xie, Yi Zhang, Bing Wan, Yanyun Zhang

Research output: Contribution to journalArticlepeer-review

74 Scopus citations


Fulminant hepatic failure (FHF) is a clinical syndrome characterized by sudden and severe impairment of liver function. Mesenchymal stem cells (MSCs) have been proposed as a promising therapeutic approach for FHF. In this study we used Propionibacterium acnes (P. acnes)-primed, lipopolysaccharide (LPS)-induced liver injury in mice as an animal model of human FHF. We demonstrated that administration of MSCs significantly ameliorated liver injury and improved the survival rates of mice subjected to P. acnes plus LPS-induced FHF. Allogeneic MSCs showed similar treatment efficacy as autologous MSCs did in FHF. Treatment efficacy of MSCs could be attributed to decreased infiltration and activation of CD4+ T cells in the liver, inhibition of T helper 1 cells, and induction of regulatory T cells (Tregs). Moreover, decreased DNA copies of P. acnes were detected in the liver of MSC-treated mice. Intriguingly, a distinct liver population of CD11c+MHCIIhiCD80loCD86lo regulatory dendritic cells (DCs) was induced by MSCs. Moreover, these DCs induced Treg differentiation through transforming growth factor-β production. Further mechanistic studies demonstrated that MSC-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 phosphoinositide 3-kinase-dependent manner. Conclusion: MSCs induce regulatory DCs from CD11c+B220- DC precursors. This study elucidates an immunoregulatory mechanism of MSCs and lays a foundation for application of MSCs in FHF therapy.

Original languageEnglish (US)
Pages (from-to)671-682
Number of pages12
Issue number2
StatePublished - Feb 2014
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Hepatology


Dive into the research topics of 'Mesenchymal stem cells alleviate bacteria-induced liver injury in mice by inducing regulatory dendritic cells'. Together they form a unique fingerprint.

Cite this