Loss of Rictor in Monocyte/Macrophages Suppresses Their Proliferation and Viability Reducing Atherosclerosis in LDLR Null Mice

Frontiers in Immunology
Vladimir R BabaevMacRae F Linton

Abstract

Rictor is an essential component of mammalian target of rapamycin (mTOR) complex 2 (mTORC2), a conserved serine/threonine kinase that may play a role in cell proliferation, survival and innate or adaptive immune responses. Genetic loss of Rictor inactivates mTORC2, which directly activates Akt S473 phosphorylation and promotes pro-survival cell signaling and proliferation. To study the role of mTORC2 signaling in monocytes and macrophages, we generated mice with myeloid lineage-specific Rictor deletion (MRictor-/-). These MRictor-/- mice exhibited dramatic reductions of white blood cells, B-cells, T-cells, and monocytes but had similar levels of neutrophils compared to control Rictor flox-flox (Rictorfl/fl) mice. MRictor-/- bone marrow monocytes and peritoneal macrophages expressed reduced levels of mTORC2 signaling and decreased Akt S473 phosphorylation, and they displayed significantly less proliferation than control Rictorfl/fl cells. In addition, blood monocytes and peritoneal macrophages isolated from MRictor-/- mice were significantly more sensitive to pro-apoptotic stimuli. In response to LPS, MRictor-/- macrophages exhibited the M1 phenotype with higher levels of pro-inflammatory gene expression and lower levels of Il10...Continue Reading

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Citations

Jun 5, 2019·International Journal of Molecular Sciences·MacRae F LintonVladimir R Babaev
Jan 26, 2020·International Journal of Molecular Sciences·Jiansheng HuangHui Huang
Nov 30, 2019·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Xiao-Lin LiuJian-Gao Fan
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Nov 23, 2021·Frontiers in Cell and Developmental Biology·Fredrick J RosarioThomas Jansson

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Methods Mentioned

BETA
Protein
electrophoresis
Flow Cytometry
PCR
histone acetylation

Software Mentioned

FACS DiVa
GraphPad Prizm
ImageJ
SPSS Statistics Premium

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