PMID- 22705178
OWN - NLM
STAT- MEDLINE
DCOM- 20121217
LR  - 20240213
IS  - 1528-0012 (Electronic)
IS  - 0016-5085 (Print)
IS  - 0016-5085 (Linking)
VI  - 143
IP  - 4
DP  - 2012 Oct
TI  - Dendritic cell populations with different concentrations of lipid regulate 
      tolerance and immunity in mouse and human liver.
PG  - 1061-72
LID - S0016-5085(12)00819-0 [pii]
LID - 10.1053/j.gastro.2012.06.003 [doi]
AB  - BACKGROUND & AIMS: Immune cells of the liver must be able to recognize and react 
      to pathogens yet remain tolerant to food molecules and other nonpathogens. 
      Dendritic cells (DCs) are believed to contribute to hepatic tolerance. Lipids 
      have been implicated in dysfunction of DCs in cancer. Therefore, we investigated 
      whether high lipid content in liver DCs affects induction of tolerance. METHODS: 
      Mouse and human hepatic nonparenchymal cells were isolated by mechanical and 
      enzymatic digestion. DCs were purified by fluorescence-activated cell sorting or 
      with immunomagnetic beads. DC lipid content was assessed by flow cytometry, 
      immune fluorescence, and electron microscopy and by measuring intracellular 
      component lipids. DC activation was determined from surface phenotype and 
      cytokine profile. DC function was assessed in T-cell, natural killer (NK) cell, 
      and NKT cell coculture assays as well as in vivo. RESULTS: We observed 2 distinct 
      populations of hepatic DCs in mice and humans based on their lipid content and 
      expression of markers associated with adipogenesis and lipid metabolism. This 
      lipid-based dichotomy in DCs was unique to the liver and specific to DCs compared 
      with other hepatic immune cells. However, rather than mediate tolerance, the 
      liver DC population with high concentrations of lipid was immunogenic in multiple 
      models; they activated T cells, NK cells, and NKT cells. Conversely, liver DCs 
      with low levels of lipid induced regulatory T cells, anergy to cancer, and oral 
      tolerance. The immunogenicity of lipid-rich liver DCs required their secretion of 
      tumor necrosis factor alpha and was directly related to their high lipid content; 
      blocking DC synthesis of fatty acids or inhibiting adipogenesis (by reducing 
      endoplasmic reticular stress) reduced DC immunogenicity. CONCLUSIONS: Human and 
      mouse hepatic DCs are composed of distinct populations that contain different 
      concentrations of lipid, which regulates immunogenic versus tolerogenic responses 
      in the liver.
CI  - Copyright (c) 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.
FAU - Ibrahim, Junaid
AU  - Ibrahim J
AD  - S. Arthur Localio Laboratory, Department of Surgery, New York University School 
      of Medicine, New York, New York 10016, USA.
FAU - Nguyen, Andrew H
AU  - Nguyen AH
FAU - Rehman, Adeel
AU  - Rehman A
FAU - Ochi, Atsuo
AU  - Ochi A
FAU - Jamal, Mohsin
AU  - Jamal M
FAU - Graffeo, Christopher S
AU  - Graffeo CS
FAU - Henning, Justin R
AU  - Henning JR
FAU - Zambirinis, Constantinos P
AU  - Zambirinis CP
FAU - Fallon, Nina C
AU  - Fallon NC
FAU - Barilla, Rocky
AU  - Barilla R
FAU - Badar, Sana
AU  - Badar S
FAU - Mitchell, Aaron
AU  - Mitchell A
FAU - Rao, Raghavendra S
AU  - Rao RS
FAU - Acehan, Devrim
AU  - Acehan D
FAU - Frey, Alan B
AU  - Frey AB
FAU - Miller, George
AU  - Miller G
LA  - eng
GR  - CA108573/CA/NCI 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
GR  - R01 CA108573/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120612
PL  - United States
TA  - Gastroenterology
JT  - Gastroenterology
JID - 0374630
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, CD1d)
RN  - 0 (B7-1 Antigen)
RN  - 0 (B7-2 Antigen)
RN  - 0 (CD11b Antigen)
RN  - 0 (CD40 Antigens)
RN  - 0 (Lipids)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - EC 3.1.3.48 (Leukocyte Common Antigens)
SB  - IM
MH  - Adipogenesis
MH  - Animals
MH  - Antigens, CD/*metabolism
MH  - Antigens, CD1d/metabolism
MH  - Apoptosis
MH  - B7-1 Antigen/metabolism
MH  - B7-2 Antigen/metabolism
MH  - CD11b Antigen/metabolism
MH  - CD40 Antigens/metabolism
MH  - Cells, Cultured
MH  - Dendritic Cells/chemistry/*immunology/*metabolism
MH  - Humans
MH  - Immune Tolerance
MH  - Intercellular Adhesion Molecule-1/metabolism
MH  - Killer Cells, Natural/physiology
MH  - Leukocyte Common Antigens/metabolism
MH  - Lipid Metabolism
MH  - Lipids/*analysis
MH  - Liver/chemistry/*immunology/*metabolism
MH  - Lymphocyte Activation
MH  - Mice
MH  - Natural Killer T-Cells/physiology
MH  - Phenotype
MH  - T-Lymphocytes/physiology
MH  - T-Lymphocytes, Regulatory/physiology
MH  - Tumor Necrosis Factor-alpha/metabolism
PMC - PMC3459067
MID - NIHMS387347
EDAT- 2012/06/19 06:00
MHDA- 2012/12/18 06:00
PMCR- 2013/10/01
CRDT- 2012/06/19 06:00
PHST- 2012/01/11 00:00 [received]
PHST- 2012/05/07 00:00 [revised]
PHST- 2012/06/08 00:00 [accepted]
PHST- 2012/06/19 06:00 [entrez]
PHST- 2012/06/19 06:00 [pubmed]
PHST- 2012/12/18 06:00 [medline]
PHST- 2013/10/01 00:00 [pmc-release]
AID - S0016-5085(12)00819-0 [pii]
AID - 10.1053/j.gastro.2012.06.003 [doi]
PST - ppublish
SO  - Gastroenterology. 2012 Oct;143(4):1061-72. doi: 10.1053/j.gastro.2012.06.003. 
      Epub 2012 Jun 12.