PMID- 31155984
OWN - NLM
STAT- MEDLINE
DCOM- 20191209
LR  - 20231217
IS  - 1532-2513 (Electronic)
IS  - 0892-3973 (Print)
IS  - 0892-3973 (Linking)
VI  - 41
IP  - 3
DP  - 2019 Jun
TI  - Inhibition of fatty acid metabolism by etomoxir or TOFA suppresses murine 
      dendritic cell activation without affecting viability.
PG  - 361-369
LID - 10.1080/08923973.2019.1616754 [doi]
AB  - Objective: Dendritic cells (DCs) are important players in immunity against 
      pathogens, but overactive DCs have been implicated in autoimmune diseases, like 
      lupus, in which a paucity of targeted therapies remains. Recent research shows 
      that DCs upregulate their immunometabolism when activating. We explored whether 
      modulating fatty acid (FA) metabolism needed for oxidative phosphorylation can 
      affect the activation of two main DC subsets. Material and methods: Sorted murine 
      plasmacytoid DCs (pDCs) and conventional DCs (cDCs), generated in FLT3-L medium, 
      were treated with etomoxir, an inhibitor of FA oxidation, or TOFA, an inhibitor 
      of FA synthesis, then stimulated with TLR9 agonist CpGA. Surface activation 
      markers and viability were analyzed by flow cytometry, cytokine, and chemokine 
      production and were measured by ELISA. Results: Modulation of FA metabolism 
      suppressed the upregulation of costimulatory molecules and the production of 
      proinflammatory cytokine IL-6 and type I Interferon-dependent chemokine CXCL10 by 
      both subsets of DCs, without affecting DC viability, neither of resting DCs or 
      upon activation. Etomoxir inhibited pDCs at lower doses than cDCs, suggesting 
      that pDCs may be more susceptible to FA metabolic modulation. Conclusions: Both 
      cDCs, the primary antigen presenting cell, and pDCs, the primary type I IFN 
      producer, exhibit a suppressed ability to activate but normal viability when 
      their FA metabolism is inhibited by etomoxir or TOFA. Our findings indicate that 
      FA metabolism plays an important role in the activation of both pDCs and cDCs and 
      suggest that its modulation is an exploitable therapeutic target to suppress DC 
      activation in inflammation or autoimmunity.
FAU - Qiu, Connie C
AU  - Qiu CC
AUID- ORCID: 0000-0002-1623-9871
AD  - a Laboratory of Dendritic Cell Biology, Department of Microbiology & Immunology , 
      Lewis Katz School of Medicine at Temple University , Philadelphia , PA , USA.
FAU - Atencio, Atilio E
AU  - Atencio AE
AD  - a Laboratory of Dendritic Cell Biology, Department of Microbiology & Immunology , 
      Lewis Katz School of Medicine at Temple University , Philadelphia , PA , USA.
FAU - Gallucci, Stefania
AU  - Gallucci S
AUID- ORCID: 0000-0003-4737-8003
AD  - a Laboratory of Dendritic Cell Biology, Department of Microbiology & Immunology , 
      Lewis Katz School of Medicine at Temple University , Philadelphia , PA , USA.
LA  - eng
GR  - R21 AI119947/AI/NIAID NIH HHS/United States
PT  - Journal Article
DEP - 20190602
PL  - England
TA  - Immunopharmacol Immunotoxicol
JT  - Immunopharmacology and immunotoxicology
JID - 8800150
RN  - 0 (Cytokines)
RN  - 0 (Epoxy Compounds)
RN  - 0 (Fatty Acids)
RN  - 0 (Furans)
RN  - 0 (Tlr9 protein, mouse)
RN  - 0 (Toll-Like Receptor 9)
RN  - 54857-86-2 (5-(tetradecyloxy)-2-furancarboxylic acid)
RN  - MSB3DD2XP6 (etomoxir)
SB  - IM
MH  - Animals
MH  - Cell Survival/drug effects/immunology
MH  - Cytokines/immunology
MH  - Dendritic Cells/cytology/*immunology
MH  - Epoxy Compounds/*pharmacology
MH  - Fatty Acids/*immunology
MH  - Furans/*pharmacology
MH  - Mice
MH  - Toll-Like Receptor 9/immunology
PMC - PMC10724852
MID - NIHMS1822362
OTO - NOTNLM
OT  - 5-(Tetradecyloxy)-2-furoic Acid
OT  - Dendritic cell activation
OT  - TOFA
OT  - conventional dendritic cell
OT  - etomoxir
OT  - fatty acid oxidation
OT  - fatty acid synthase
OT  - immunometabolism
OT  - plasmacytoid dendritic cell
OT  - pro-inflammatory cytokines
OT  - systemic lupus erythematosus
COIS- Declaration of interest/disclosure No financial benefit has arisen from the 
      findings in this research. No conflicts of interest are reported by any of the 
      authors.
EDAT- 2019/06/04 06:00
MHDA- 2019/12/18 06:00
PMCR- 2023/12/16
CRDT- 2019/06/04 06:00
PHST- 2019/06/04 06:00 [pubmed]
PHST- 2019/12/18 06:00 [medline]
PHST- 2019/06/04 06:00 [entrez]
PHST- 2023/12/16 00:00 [pmc-release]
AID - 10.1080/08923973.2019.1616754 [doi]
PST - ppublish
SO  - Immunopharmacol Immunotoxicol. 2019 Jun;41(3):361-369. doi: 
      10.1080/08923973.2019.1616754. Epub 2019 Jun 2.