PMID- 28108233
OWN - NLM
STAT- MEDLINE
DCOM- 20180319
LR  - 20181204
IS  - 1600-0641 (Electronic)
IS  - 0168-8278 (Linking)
VI  - 66
IP  - 6
DP  - 2017 Jun
TI  - Murine CD103(+) dendritic cells protect against steatosis progression towards 
      steatohepatitis.
PG  - 1241-1250
LID - S0168-8278(17)30012-0 [pii]
LID - 10.1016/j.jhep.2017.01.008 [doi]
AB  - BACKGROUND & AIMS: Non-alcoholic fatty liver (NAFL) is the hepatic consequence of 
      metabolic syndrome and can progress to non-alcoholic steatohepatitis (NASH). The 
      identification of molecular and cellular factors that determine the progression 
      of NASH and lead to irreversible hepatocellular damage are crucial. Dendritic 
      cells (DCs) represent a heterogeneous cell population among which CD103(+) DCs 
      play a significant role in immunity and tolerance. We aimed to clarify the role 
      of this DC subset in the pathomechanism of NASH. METHODS: Steatosis progression 
      towards steatohepatitis was analysed using multicolor FACS analyses, cytokine and 
      qPCR array in high sucrose diet (HSD) and methionine and choline deficient diet 
      (MCD) fed wild-type and basic leucine zipper transcription factor, ATF-Like-3 
      (Batf3) deficient animals, which lack CD103(+) DCs (classical type-1 DC, cDC1s). 
      RESULTS: Metabolic challenge of Batf3(-/-) animals resulted in the progression of 
      steatosis towards steatohepatitis, manifesting by an increased influx of 
      inflammatory cells into the liver and elevated inflammatory cytokine production 
      of myeloid cells upon innate stimuli. However, the lack of cDC1s did not affect 
      cellular apoptosis and fibrosis progression but altered genes involved in lipid 
      metabolism. The adoptive transfer of CD103(+) cDC1s to Batf3 deficient animals 
      reversed these observed changes and more importantly could attenuate cellular 
      damage and inflammation in established murine steatohepatitis. CONCLUSION: Here, 
      we have identified the murine CD103(+) cDC1s as a protective DC subtype that 
      influences the pro-anti-inflammatory balance and protects the liver from 
      metabolic damage. As guardians of liver integrity, they play a key role in the 
      inflammatory process during the development of steatohepatitis in mice. LAY 
      SUMMARY: Non-alcoholic fatty liver (NAFL) is the hepatic consequence of metabolic 
      syndrome and can lead to non-alcoholic steatohepatitis (NASH). The current study 
      demonstrated that a specific murine dendritic cell subtype possesses a potent 
      regulatory role to influence the inflammatory milieu of the liver in this 
      process.
CI  - Copyright (c) 2017 European Association for the Study of the Liver. Published by 
      Elsevier B.V. All rights reserved.
FAU - Heier, Eva-Carina
AU  - Heier EC
AD  - Department of Medicine II, Saarland University Medical Center, Homburg, Germany.
FAU - Meier, Anna
AU  - Meier A
AD  - Department of Medicine II, Saarland University Medical Center, Homburg, Germany.
FAU - Julich-Haertel, Henrike
AU  - Julich-Haertel H
AD  - Department of Medicine II, Saarland University Medical Center, Homburg, Germany.
FAU - Djudjaj, Sonja
AU  - Djudjaj S
AD  - Institute of Pathology and Department of Medicine II, University Hospital, RWTH 
      Aachen, Germany.
FAU - Rau, Monica
AU  - Rau M
AD  - Department of Internal Medicine II, University Hospital Wurzburg, Germany.
FAU - Tschernig, Thomas
AU  - Tschernig T
AD  - Insitute of Anatomy and Cell Biology, University of Saarland, Germany.
FAU - Geier, Andreas
AU  - Geier A
AD  - Department of Internal Medicine II, University Hospital Wurzburg, Germany.
FAU - Boor, Peter
AU  - Boor P
AD  - Institute of Pathology and Department of Medicine II, University Hospital, RWTH 
      Aachen, Germany.
FAU - Lammert, Frank
AU  - Lammert F
AD  - Department of Medicine II, Saarland University Medical Center, Homburg, Germany.
FAU - Lukacs-Kornek, Veronika
AU  - Lukacs-Kornek V
AD  - Department of Medicine II, Saarland University Medical Center, Homburg, Germany. 
      Electronic address: lukacsver@aol.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170118
PL  - Netherlands
TA  - J Hepatol
JT  - Journal of hepatology
JID - 8503886
RN  - 0 (Antigens, CD)
RN  - 0 (Basic-Leucine Zipper Transcription Factors)
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Integrin alpha Chains)
RN  - 0 (Repressor Proteins)
RN  - 0 (SNFT protein, mouse)
RN  - 0 (alpha E integrins)
SB  - IM
CIN - J Hepatol. 2017 Jun;66(6):1120-1122. PMID: 28237398
MH  - Adoptive Transfer
MH  - Animals
MH  - Antigens, CD/*metabolism
MH  - Basic-Leucine Zipper Transcription Factors/deficiency/genetics
MH  - Cytokines/metabolism
MH  - Dendritic Cells/classification/*immunology/metabolism
MH  - Disease Progression
MH  - Inflammation Mediators/metabolism
MH  - Integrin alpha Chains/*metabolism
MH  - Lipid Metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Non-alcoholic Fatty Liver Disease/etiology/immunology/*prevention & control
MH  - Repressor Proteins/deficiency/genetics
OTO - NOTNLM
OT  - Dendritic cells
OT  - Inflammation
OT  - NASH
OT  - Steatosis
EDAT- 2017/01/22 06:00
MHDA- 2018/03/20 06:00
CRDT- 2017/01/22 06:00
PHST- 2016/07/18 00:00 [received]
PHST- 2017/01/03 00:00 [revised]
PHST- 2017/01/04 00:00 [accepted]
PHST- 2017/01/22 06:00 [pubmed]
PHST- 2018/03/20 06:00 [medline]
PHST- 2017/01/22 06:00 [entrez]
AID - S0168-8278(17)30012-0 [pii]
AID - 10.1016/j.jhep.2017.01.008 [doi]
PST - ppublish
SO  - J Hepatol. 2017 Jun;66(6):1241-1250. doi: 10.1016/j.jhep.2017.01.008. Epub 2017 
      Jan 18.