Loss of mTORC2-induced metabolic reprogramming in monocytes uncouples migration and maturation from production of proinflammatory mediators
| Autor: | Lamya Yamani, Frances R. Balkwill, Federica M. Marelli-Berg, Juho Vuononvirta, Melania Capasso, Eleanor J. Ward, Suchita Nadkarni, Maryam Jangani |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Immunology
Inflammation Mechanistic Target of Rapamycin Complex 2 macrophage Biology mTORC2 Monocytes Proinflammatory cytokine cell metabolism ddc:570 medicine Immunology and Allergy Macrophage Protein kinase B Mechanistic target of rapamycin Sirolimus Monocyte Macrophages Cell Biology Cell biology metabolism [Rapamycin-Insensitive Companion of mTOR Protein] medicine.anatomical_structure Rapamycin-Insensitive Companion of mTOR Protein metabolism [Proto-Oncogene Proteins c-akt] monocyte biology.protein Phosphorylation metabolism [Macrophages] metabolism [Mechanistic Target of Rapamycin Complex 2] medicine.symptom Proto-Oncogene Proteins c-akt metabolism metabolism [Monocytes] |
| Zdroj: | Journal of leukocyte biology 111(5), 967-980 (2022). doi:10.1002/JLB.1A0920-588R |
| DOI: | 10.1002/JLB.1A0920-588R |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|