Dendritic cell regulation of carbon tetrachloride-induced murine liver fibrosis regression
Open Access
- 24 August 2011
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Journal of Hepatology
- Vol. 55 (1), 244-255
- https://doi.org/10.1002/hep.24621
Abstract
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)This publication has 56 references indexed in Scilit:
- Unravelling mononuclear phagocyte heterogeneityNature Reviews Immunology, 2010
- Outcome of sustained virological responders with histologically advanced chronic hepatitis CJournal of Hepatology, 2010
- Invariant Natural Killer T Cells Suppress the Neutrophil Inflammatory Response in a Mouse Model of Cholestatic Liver DamageGastroenterology, 2009
- Diverse roles of invariant natural killer T cells in liver injury and fibrosis induced by carbon tetrachlorideJournal of Hepatology, 2008
- Immune Interactions in Hepatic FibrosisClinics in Liver Disease, 2008
- Senescence of Activated Stellate Cells Limits Liver FibrosisCell, 2008
- Mechanisms of Hepatic FibrogenesisGastroenterology, 2008
- Dendritic Cells Prime Natural Killer Cells by trans-Presenting Interleukin 15Immunity, 2007
- Identification, activation, and selectivein vivoablation of mouse NK cells via NKp46Proceedings of the National Academy of Sciences of the United States of America, 2007
- Mouse and human dendritic cell subtypesNature Reviews Immunology, 2002