Dendritic cell regulation of carbon tetrachloride–induced murine liver fibrosis regression§


  • Potential conflict of interest: Nothing to report.

  • Supported by funds from the Department of Medicine, Mount Sinai School of Medicine, and the American Association for the Study of Liver Diseases Liver Scholar Award (to C. A.); National Institutes of Health Grants DK56621 and 1K05AA018408-01 (to S. L. F.); and National Institutes of Health Grants CA112100 and HL086899 (to M. M.).

  • §

    Portions of this study were presented in abstract form at the 2008 American Association for the Study of Liver Diseases annual meeting.


Although hepatic fibrosis typically follows chronic inflammation, fibrosis will often regress after cessation of liver injury. In this study, we examined whether liver dendritic cells (DCs) play a role in liver fibrosis regression using carbon tetrachloride to induce liver injury. We examined DC dynamics during fibrosis regression and their capacity to modulate liver fibrosis regression upon cessation of injury. We show that conditional DC depletion soon after discontinuation of the liver insult leads to delayed fibrosis regression and reduced clearance of activated hepatic stellate cells, the key fibrogenic cell in the liver. Conversely, DC expansion induced either by Flt3L (fms-like tyrosine kinase-3 ligand) or adoptive transfer of purified DCs accelerates liver fibrosis regression. DC modulation of fibrosis was partially dependent on matrix metalloproteinase (MMP)-9, because MMP-9 inhibition abolished the Flt3L-mediated effect and the ability of transferred DCs to accelerate fibrosis regression. In contrast, transfer of DCs from MMP-9–deficient mice failed to improve fibrosis regression. Conclusion: Taken together, these results suggest that DCs increase fibrosis regression and that the effect is correlated with their production of MMP-9. The results also suggest that Flt3L treatment during fibrosis resolution merits evaluation to accelerate regression of advanced liver fibrosis. (HEPATOLOGY 2012;55:243–255)