TY  - JOUR
AU  - Jangani, Maryam
AU  - Vuononvirta, Juho
AU  - Yamani, Lamya
AU  - Ward, Eleanor
AU  - Capasso, Melania
AU  - Nadkarni, Suchita
AU  - Balkwill, Frances
AU  - Marelli-Berg, Federica
TI  - Loss of mTORC2-induced metabolic reprogramming in monocytes uncouples migration and maturation from production of proinflammatory mediators.
JO  - Journal of leukocyte biology
VL  - 111
IS  - 5
SN  - 1938-3673
CY  - Hoboken, NJ
PB  - Wiley
M1  - DZNE-2021-01579
SP  - 967-980
PY  - 2022
N1  - (CC BY)
AB  - 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.
KW  - Macrophages: metabolism
KW  - Mechanistic Target of Rapamycin Complex 2: metabolism
KW  - Monocytes: metabolism
KW  - Proto-Oncogene Proteins c-akt: metabolism
KW  - Rapamycin-Insensitive Companion of mTOR Protein: metabolism
KW  - Sirolimus
KW  - cell metabolism (Other)
KW  - mTORC2 (Other)
KW  - macrophage (Other)
KW  - metabolism (Other)
KW  - monocyte (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:34585416
DO  - DOI:10.1002/JLB.1A0920-588R
UR  - https://pub.dzne.de/record/162927
ER  -