PMID- 34431087
OWN - NLM
STAT- MEDLINE
DCOM- 20220221
LR  - 20220910
IS  - 1365-2567 (Electronic)
IS  - 0019-2805 (Print)
IS  - 0019-2805 (Linking)
VI  - 165
IP  - 1
DP  - 2022 Jan
TI  - Metabolomic and lipidomic signatures associated with activation of human cDC1 
      (BDCA3(+) /CD141(+) ) dendritic cells.
PG  - 99-109
LID - 10.1111/imm.13409 [doi]
AB  - Dendritic cells (DCs) bridge the connection between innate and adaptive immunity. 
      DCs present antigens to T cells and stimulate potent cytotoxic T-cell responses. 
      Metabolic reprogramming is critical for DC development and activation; however, 
      metabolic adaptations and regulation in DC subsets remains largely 
      uncharacterized. Here, we mapped metabolomic and lipidomic signatures associated 
      with the activation phenotype of human conventional DC type 1, a DC subset 
      specialized in cross-presentation and therefore of major importance for the 
      stimulation of CD8(+) T cells. Our metabolomics and lipidomic analyses showed 
      that Toll-like receptor (TLR) stimulation altered glycerolipids and amino acids 
      in cDC1. Poly I:C or pRNA stimulation reduced triglycerides and cholesterol 
      esters, as well as various amino acids. Moreover, TLR stimulation reduced 
      expression of glycolysis-regulating genes and did not induce glycolysis. 
      Conversely, cDC1 exhibited increased mitochondrial content and oxidative 
      phosphorylation (OXPHOS) upon TLR3 or TLR7/8 stimulation. Our findings highlight 
      the metabolic adaptations required for cDC1 maturation.
CI  - (c) 2021 The Authors. Immunology published by John Wiley & Sons Ltd.
FAU - Basit, Farhan
AU  - Basit F
AUID- ORCID: 0000-0001-8205-8393
AD  - Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, 
      Radboudumc, Nijmegen, The Netherlands.
FAU - van Oorschot, Tom
AU  - van Oorschot T
AD  - Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, 
      Radboudumc, Nijmegen, The Netherlands.
FAU - van Buggenum, Jessie
AU  - van Buggenum J
AD  - Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, 
      Radboudumc, Nijmegen, The Netherlands.
FAU - Derks, Rico J E
AU  - Derks RJE
AD  - Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, 
      The Netherlands.
FAU - Kostidis, Sarantos
AU  - Kostidis S
AD  - Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, 
      The Netherlands.
FAU - Giera, Martin
AU  - Giera M
AD  - Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, 
      The Netherlands.
FAU - de Vries, I Jolanda M
AU  - de Vries IJM
AD  - Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, 
      Radboudumc, Nijmegen, The Netherlands.
AD  - Department of Medical Oncology, Radboudumc, Nijmegen, The Netherlands.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210907
PL  - England
TA  - Immunology
JT  - Immunology
JID - 0374672
RN  - 0 (Amino Acids)
RN  - 0 (Biomarkers)
RN  - 0 (Cytokines)
RN  - 0 (Lipopolysaccharide Receptors)
RN  - 0 (THBD protein, human)
RN  - 0 (Thrombomodulin)
RN  - 0 (Toll-Like Receptors)
SB  - IM
MH  - Amino Acids/metabolism
MH  - Biomarkers
MH  - Cytokines/metabolism
MH  - Dendritic Cells/*immunology/*metabolism
MH  - Humans
MH  - Immunophenotyping
MH  - *Lipid Metabolism
MH  - *Lipidomics/methods
MH  - Lipopolysaccharide Receptors/metabolism
MH  - Metabolic Networks and Pathways
MH  - Metabolome
MH  - Metabolomics
MH  - Oxidative Phosphorylation
MH  - Thrombomodulin/metabolism
MH  - Toll-Like Receptors/metabolism
PMC - PMC9426619
OTO - NOTNLM
OT  - BDCA3
OT  - dendritic cell activation
OT  - lipid mediators
OT  - metabolomics
COIS- The authors have no competing interests to declare.
EDAT- 2021/08/26 06:00
MHDA- 2022/02/22 06:00
PMCR- 2021/09/07
CRDT- 2021/08/25 06:36
PHST- 2021/06/17 00:00 [revised]
PHST- 2021/01/07 00:00 [received]
PHST- 2021/07/06 00:00 [accepted]
PHST- 2021/08/26 06:00 [pubmed]
PHST- 2022/02/22 06:00 [medline]
PHST- 2021/08/25 06:36 [entrez]
PHST- 2021/09/07 00:00 [pmc-release]
AID - IMM13409 [pii]
AID - 10.1111/imm.13409 [doi]
PST - ppublish
SO  - Immunology. 2022 Jan;165(1):99-109. doi: 10.1111/imm.13409. Epub 2021 Sep 7.