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000162927 0247_ $$2doi$$a10.1002/JLB.1A0920-588R
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000162927 037__ $$aDZNE-2021-01579
000162927 041__ $$aEnglish
000162927 082__ $$a570
000162927 1001_ $$aJangani, Maryam$$b0
000162927 245__ $$aLoss of mTORC2-induced metabolic reprogramming in monocytes uncouples migration and maturation from production of proinflammatory mediators.
000162927 260__ $$aHoboken, NJ$$bWiley$$c2022
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000162927 520__ $$aMonocyte 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.
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000162927 650_7 $$2Other$$acell metabolism
000162927 650_7 $$2Other$$amTORC2
000162927 650_7 $$2Other$$amacrophage
000162927 650_7 $$2Other$$ametabolism
000162927 650_7 $$2Other$$amonocyte
000162927 650_2 $$2MeSH$$aMacrophages: metabolism
000162927 650_2 $$2MeSH$$aMechanistic Target of Rapamycin Complex 2: metabolism
000162927 650_2 $$2MeSH$$aMonocytes: metabolism
000162927 650_2 $$2MeSH$$aProto-Oncogene Proteins c-akt: metabolism
000162927 650_2 $$2MeSH$$aRapamycin-Insensitive Companion of mTOR Protein: metabolism
000162927 650_2 $$2MeSH$$aSirolimus
000162927 7001_ $$aVuononvirta, Juho$$b1
000162927 7001_ $$aYamani, Lamya$$b2
000162927 7001_ $$aWard, Eleanor$$b3
000162927 7001_ $$0P:(DE-2719)2811780$$aCapasso, Melania$$b4$$udzne
000162927 7001_ $$aNadkarni, Suchita$$b5
000162927 7001_ $$aBalkwill, Frances$$b6
000162927 7001_ $$0P:(DE-HGF)0$$aMarelli-Berg, Federica$$b7$$eCorresponding author
000162927 773__ $$0PERI:(DE-600)2026833-6$$a10.1002/JLB.1A0920-588R$$gp. JLB.1A0920-588R$$n5$$p967-980$$tJournal of leukocyte biology$$v111$$x1938-3673$$y2022
000162927 8564_ $$uhttps://jlb.onlinelibrary.wiley.com/doi/10.1002/JLB.1A0920-588R
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