Loss of mTORC2-induced metabolic reprogramming in monocytes uncouples migration and maturation from production of proinflammatory mediators.
cell metabolism
mTORC2
macrophage
metabolism
monocyte
Journal
Journal of leukocyte biology
ISSN: 1938-3673
Titre abrégé: J Leukoc Biol
Pays: England
ID NLM: 8405628
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
pubmed:
30
9
2021
medline:
26
4
2022
entrez:
29
9
2021
Statut:
ppublish
Résumé
Monocyte migration to the sites of inflammation and maturation into macrophages are key steps for their immune effector function. Here, we show that mechanistic target of rapamycin complex 2 (mTORC2)-dependent Akt activation is instrumental for metabolic reprogramming at the early stages of macrophage-mediated immunity. Despite an increased production of proinflammatory mediators, monocytes lacking expression of the mTORC2 component Rictor fail to efficiently migrate to inflammatory sites and fully mature into macrophages, resulting in reduced inflammatory responses in vivo. The mTORC2-dependent phosphorylation of Akt is instrumental for the enhancement of glycolysis and mitochondrial respiration, required to sustain monocyte maturation and motility. These observations are discussed in the context of therapeutic strategies aimed at selective inhibition of mTORC2 activity.
Identifiants
pubmed: 34585416
doi: 10.1002/JLB.1A0920-588R
doi:
Substances chimiques
Rapamycin-Insensitive Companion of mTOR Protein
0
Mechanistic Target of Rapamycin Complex 2
EC 2.7.11.1
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Sirolimus
W36ZG6FT64
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
967-980Subventions
Organisme : British Heart Foundation
ID : RG/09/002/26425
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/16/18/31973
Pays : United Kingdom
Organisme : British Heart Foundation
ID : PG/14/84/31136
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 14355
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 12888
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/14/2/30616
Pays : United Kingdom
Organisme : British Heart Foundation
ID : CH/15/2/32064
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0901084
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/11/64/28945
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/20/8/34995
Pays : United Kingdom
Informations de copyright
© 2021 The Authors. Journal of Leukocyte Biology published by Wiley Periodicals LLC on behalf of Society for Leukocyte Biology.
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