PMID- 23322710
OWN - NLM
STAT- MEDLINE
DCOM- 20140116
LR  - 20211021
IS  - 1527-3350 (Electronic)
IS  - 0270-9139 (Print)
IS  - 0270-9139 (Linking)
VI  - 58
IP  - 2
DP  - 2013 Aug
TI  - Dendritic cells limit fibroinflammatory injury in nonalcoholic steatohepatitis in 
      mice.
PG  - 589-602
LID - 10.1002/hep.26267 [doi]
AB  - 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. CONCLUSION: Our findings 
      support a role for DCs in modulating NASH. Targeting DC functional properties may 
      hold promise for therapeutic intervention in NASH.
CI  - Copyright (c) 2013 American Association for the Study of Liver Diseases.
FAU - Henning, Justin R
AU  - Henning JR
AD  - Department of Surgery, S. Arthur Localio Laboratory, New York University School 
      of Medicine, New York, NY 10016, USA.
FAU - Graffeo, Christopher S
AU  - Graffeo CS
FAU - Rehman, Adeel
AU  - Rehman A
FAU - Fallon, Nina C
AU  - Fallon NC
FAU - Zambirinis, Constantinos P
AU  - Zambirinis CP
FAU - Ochi, Atsuo
AU  - Ochi A
FAU - Barilla, Rocky
AU  - Barilla R
FAU - Jamal, Mohsin
AU  - Jamal M
FAU - Deutsch, Michael
AU  - Deutsch M
FAU - Greco, Stephanie
AU  - Greco S
FAU - Ego-Osuala, Melvin
AU  - Ego-Osuala M
FAU - Bin-Saeed, Usama
AU  - Bin-Saeed U
FAU - Rao, Raghavendra S
AU  - Rao RS
FAU - Badar, Sana
AU  - Badar S
FAU - Quesada, Juan P
AU  - Quesada JP
FAU - Acehan, Devrim
AU  - Acehan D
FAU - Miller, George
AU  - Miller G
LA  - eng
GR  - UL1 RR029893/RR/NCRR NIH HHS/United States
GR  - 1UL1RR029893/RR/NCRR NIH HHS/United States
GR  - R21 CA155649/CA/NCI NIH HHS/United States
GR  - CA155649/CA/NCI NIH HHS/United States
GR  - K08 DK085278/DK/NIDDK NIH HHS/United States
GR  - DK085278/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130624
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (Toll-Like Receptors)
SB  - IM
CIN - Hepatology. 2013 Aug;58(2):494-6. PMID: 23519833
CIN - Ann Hepatol. 2013 May-Jun;12(3):508-9. PMID: 23619272
MH  - Animals
MH  - Apoptosis/physiology
MH  - CD8-Positive T-Lymphocytes/pathology
MH  - Cell Communication/*physiology
MH  - Cells, Cultured
MH  - Dendritic Cells/pathology/*physiology
MH  - Disease Models, Animal
MH  - *Disease Progression
MH  - Fatty Liver/pathology/*physiopathology
MH  - Kupffer Cells/pathology
MH  - Liver/*physiopathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Necrosis/physiopathology
MH  - Neutrophils/pathology
MH  - Toll-Like Receptors/physiology
PMC - PMC3638069
MID - NIHMS436339
EDAT- 2013/01/17 06:00
MHDA- 2014/01/17 06:00
PMCR- 2014/08/01
CRDT- 2013/01/17 06:00
PHST- 2012/06/04 00:00 [received]
PHST- 2012/12/21 00:00 [accepted]
PHST- 2013/01/17 06:00 [entrez]
PHST- 2013/01/17 06:00 [pubmed]
PHST- 2014/01/17 06:00 [medline]
PHST- 2014/08/01 00:00 [pmc-release]
AID - 10.1002/hep.26267 [doi]
PST - ppublish
SO  - Hepatology. 2013 Aug;58(2):589-602. doi: 10.1002/hep.26267. Epub 2013 Jun 24.