title: Dendritic cell regulation of carbon tetrachloride-induced murine liver fibrosis regression.
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.
  
  
  CONCLUSIONS
  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.
authors: Division of Liver Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA.
authors: Jingjing
authors: J
authors: Jiao
authors: David
authors: D
authors: Sastre
authors: Maria Isabel
authors: MI
authors: Fiel
authors: Ursula E
authors: UE
authors: Lee
authors: Zahra
authors: Z
authors: Ghiassi-Nejad
authors: Florent
authors: F
authors: Ginhoux
authors: Eric
authors: E
authors: Vivier
authors: Scott L
authors: SL
authors: Friedman
authors: Miriam
authors: M
authors: Merad
authors: Costica
authors: C
authors: Aloman
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology* / Q000637:transplantation; D005260:Female; D007694:Killer Cells, Natural / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D008115:Liver Regeneration / Q000502:physiology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008565:Membrane Proteins / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000473:pathology; D010641:Phenotype
chemical_list: D000276:Adjuvants, Immunologic; D008565:Membrane Proteins; C084881:flt3 ligand protein; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse