PMID- 29941886
OWN - NLM
STAT- MEDLINE
DCOM- 20181218
LR  - 20190625
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 9
IP  - 1
DP  - 2018 Jun 25
TI  - Glycolytic metabolism is essential for CCR7 oligomerization and dendritic cell 
      migration.
PG  - 2463
LID - 10.1038/s41467-018-04804-6 [doi]
LID - 2463
AB  - Dendritic cells (DCs) are first responders of the innate immune system that 
      integrate signals from external stimuli to direct context-specific immune 
      responses. Current models suggest that an active switch from mitochondrial 
      metabolism to glycolysis accompanies DC activation to support the anabolic 
      requirements of DC function. We show that early glycolytic activation is a common 
      program for both strong and weak stimuli, but that weakly activated DCs lack 
      long-term HIF-1alpha-dependent glycolytic reprogramming and retain mitochondrial 
      oxidative metabolism. Early induction of glycolysis is associated with activation 
      of AKT, TBK, and mTOR, and sustained activation of these pathways is associated 
      with long-term glycolytic reprogramming. We show that inhibition of glycolysis 
      impaired maintenance of elongated cell shape, DC motility, CCR7 oligomerization, 
      and DC migration to draining lymph nodes. Together, our results indicate that 
      early induction of glycolysis occurs independent of pro-inflammatory phenotype, 
      and that glycolysis supports DC migratory ability regardless of mitochondrial 
      bioenergetics.
FAU - Guak, Hannah
AU  - Guak H
AD  - Goodman Cancer Research Centre, Department of Physiology, McGill University, 
      Montreal, QC, H3G 1Y6, Canada.
FAU - Al Habyan, Sara
AU  - Al Habyan S
AD  - Goodman Cancer Research Centre, Department of Oncology, McGill University, 
      Montreal, QC, H3G 1Y6, Canada.
FAU - Ma, Eric H
AU  - Ma EH
AD  - Goodman Cancer Research Centre, Department of Physiology, McGill University, 
      Montreal, QC, H3G 1Y6, Canada.
FAU - Aldossary, Haya
AU  - Aldossary H
AD  - Meakins-Christie Laboratories, Research Institute of McGill University Health 
      Center, Department of Medicine, McGill University, Montreal, H4A 3J1, QC, Canada.
AD  - Goodman Cancer Research Centre, Department of Microbiology and Immunology, McGill 
      University, Montreal, QC, H3G 1Y6, Canada.
FAU - Al-Masri, Maia
AU  - Al-Masri M
AD  - Goodman Cancer Research Centre, Department of Oncology, McGill University, 
      Montreal, QC, H3G 1Y6, Canada.
FAU - Won, So Yoon
AU  - Won SY
AD  - Goodman Cancer Research Centre, Department of Physiology, McGill University, 
      Montreal, QC, H3G 1Y6, Canada.
FAU - Ying, Thomas
AU  - Ying T
AD  - Goodman Cancer Research Centre, Department of Microbiology and Immunology, McGill 
      University, Montreal, QC, H3G 1Y6, Canada.
FAU - Fixman, Elizabeth D
AU  - Fixman ED
AD  - Meakins-Christie Laboratories, Research Institute of McGill University Health 
      Center, Department of Medicine, McGill University, Montreal, H4A 3J1, QC, Canada.
FAU - Jones, Russell G
AU  - Jones RG
AD  - Goodman Cancer Research Centre, Department of Physiology, McGill University, 
      Montreal, QC, H3G 1Y6, Canada.
FAU - McCaffrey, Luke M
AU  - McCaffrey LM
AD  - Goodman Cancer Research Centre, Department of Oncology, McGill University, 
      Montreal, QC, H3G 1Y6, Canada.
FAU - Krawczyk, Connie M
AU  - Krawczyk CM
AUID- ORCID: 0000-0002-2468-5986
AD  - Goodman Cancer Research Centre, Department of Physiology, McGill University, 
      Montreal, QC, H3G 1Y6, Canada. connie.krawczyk@mcgill.ca.
AD  - Goodman Cancer Research Centre, Department of Microbiology and Immunology, McGill 
      University, Montreal, QC, H3G 1Y6, Canada. connie.krawczyk@mcgill.ca.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180625
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (Ccr7 protein, mouse)
RN  - 0 (Receptors, CCR7)
SB  - IM
MH  - Animals
MH  - Cell Differentiation
MH  - Cell Movement/*immunology
MH  - Cell Shape/physiology
MH  - Dendritic Cells/*immunology/physiology
MH  - Female
MH  - Glycolysis/*physiology
MH  - Lymph Nodes/cytology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mitochondria/metabolism
MH  - *Oxidative Phosphorylation
MH  - Receptors, CCR7/*metabolism
PMC - PMC6018630
COIS- The authors declare no competing interests.
EDAT- 2018/06/27 06:00
MHDA- 2018/12/19 06:00
PMCR- 2018/06/25
CRDT- 2018/06/27 06:00
PHST- 2017/06/11 00:00 [received]
PHST- 2018/05/15 00:00 [accepted]
PHST- 2018/06/27 06:00 [entrez]
PHST- 2018/06/27 06:00 [pubmed]
PHST- 2018/12/19 06:00 [medline]
PHST- 2018/06/25 00:00 [pmc-release]
AID - 10.1038/s41467-018-04804-6 [pii]
AID - 4804 [pii]
AID - 10.1038/s41467-018-04804-6 [doi]
PST - epublish
SO  - Nat Commun. 2018 Jun 25;9(1):2463. doi: 10.1038/s41467-018-04804-6.