Journal Article

DZNE-2021-01579

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Loss of mTORC2-induced metabolic reprogramming in monocytes uncouples migration and maturation from production of proinflammatory mediators.

Jangani, M. ; Vuononvirta, J. ; Yamani, L. ; Ward, E. ; Capasso, M.DZNE* ; Nadkarni, S. ; Balkwill, F. ; Marelli-Berg, F. (Corresponding author)

2022
Wiley Hoboken, NJ

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Please use a persistent id in citations: doi:10.1002/JLB.1A0920-588R

Abstract: 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.

Keyword(s): Macrophages: metabolism (MeSH) ; Mechanistic Target of Rapamycin Complex 2: metabolism (MeSH) ; Monocytes: metabolism (MeSH) ; Proto-Oncogene Proteins c-akt: metabolism (MeSH) ; Rapamycin-Insensitive Companion of mTOR Protein: metabolism (MeSH) ; Sirolimus (MeSH) ; cell metabolism ; mTORC2 ; macrophage ; metabolism ; monocyte

Note: (CC BY)

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Contributing Institute(s):

1. Immune Regulation (AG Capasso)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)

Appears in the scientific report 2022

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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