title: Dendritic cells limit fibroinflammatory injury in nonalcoholic steatohepatitis in mice.
abstract: Nonalcoholic steatohepatitis (NASH) is the most common etiology of chronic liver dysfunction in the United States and can progress to cirrhosis and liver failure. Inflammatory insult resulting from fatty infiltration of the liver is central to disease pathogenesis. Dendritic cells (DCs) are antigen-presenting cells with an emerging role in hepatic inflammation. We postulated that DCs are important in the progression of NASH. We found that intrahepatic DCs expand and mature in NASH liver and assume an activated immune phenotype. However, rather than mitigating the severity of NASH, DC depletion markedly exacerbated intrahepatic fibroinflammation. Our mechanistic studies support a regulatory role for DCs in NASH by limiting sterile inflammation through their role in the clearance of apoptotic cells and necrotic debris. We found that DCs limit CD8(+) T-cell expansion and restrict Toll-like receptor expression and cytokine production in innate immune effector cells in NASH, including Kupffer cells, neutrophils, and inflammatory monocytes. Consistent with their regulatory role in NASH, during the recovery phase of disease, ablation of DC populations results in delayed resolution of intrahepatic inflammation and fibroplasia.
  
  
  CONCLUSIONS
  Our findings support a role for DCs in modulating NASH. Targeting DC functional properties may hold promise for therapeutic intervention in NASH.
authors: Department of Surgery, S. Arthur Localio Laboratory, New York University School of Medicine, New York, NY 10016, USA.
authors: Justin R
authors: JR
authors: Henning
authors: Christopher S
authors: CS
authors: Graffeo
authors: Adeel
authors: A
authors: Rehman
authors: Nina C
authors: NC
authors: Fallon
authors: Constantinos P
authors: CP
authors: Zambirinis
authors: Atsuo
authors: A
authors: Ochi
authors: Rocky
authors: R
authors: Barilla
authors: Mohsin
authors: M
authors: Jamal
authors: Michael
authors: M
authors: Deutsch
authors: Stephanie
authors: S
authors: Greco
authors: Melvin
authors: M
authors: Ego-Osuala
authors: Usama
authors: U
authors: Bin-Saeed
authors: Raghavendra S
authors: RS
authors: Rao
authors: Sana
authors: S
authors: Badar
authors: Juan P
authors: JP
authors: Quesada
authors: Devrim
authors: D
authors: Acehan
authors: George
authors: G
authors: Miller
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D002450:Cell Communication / Q000502:physiology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000473:pathology / Q000502:physiology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005234:Fatty Liver / Q000473:pathology / Q000503:physiopathology*; D007728:Kupffer Cells / Q000473:pathology; D008099:Liver / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009336:Necrosis / Q000503:physiopathology; D009504:Neutrophils / Q000473:pathology; D051193:Toll-Like Receptors / Q000502:physiology
chemical_list: D051193:Toll-Like Receptors