mTOR masters monocyte development in bone marrow by decreasing the inhibition of STAT5 on IRF8.

Blood
Yang ZhaoYong Zhao

Abstract

Monocytes and macrophages play a key role in defending pathogens, removing the dead cells or cell debris, and wound healing. The mammalian target of rapamycin (mTOR) inhibitor rapamycin (RPM) is widely used in clinics to treat patients with organ transplantation or tumors. The role of mTOR in monocyte/macrophage development remains to be clarified. Here we found that mTOR intrinsically controls monocyte/macrophage development, as evidenced by the decreased percentages and cell numbers of CD11b+F4/80+ cells resulting from mTOR inhibition in SCID mice, mTOR-deficient mice, and mixed chimera mice, and the in vitro colony formation and monocyte/macrophage induction assays. However, Lyzs-mTOR knockout mice displayed normal levels of monocytes/macrophages, indicating that mTOR is not essential for the survival and maturation of monocytes/macrophages. Further studies showed that mTOR deficiency significantly reduced macrophage colony-stimulating factor receptor CD115 expression at the transcriptional and translational levels. The molecular mechanism studies indicate that the impaired monocyte/macrophage development caused by mTOR deficiency is mainly a result of the overactivated STAT5 and subsequent downregulation of IRF8, but not th...Continue Reading

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Citations

Feb 6, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Peng WangYong Zhao
Jul 31, 2018·Journal of Immunology Research·Fan YangYong Zhao
Jun 20, 2019·Frontiers in Pharmacology·Du WuPengfei Hu
Aug 30, 2018·Biochemical Society Transactions·Natasha MalikAlison M Michie
Apr 6, 2019·Cellular & Molecular Immunology·Zhulang ChuYong Zhao
Oct 13, 2020·Frontiers in Oncology·Máté KissDamya Laoui
May 15, 2021·Immunology and Cell Biology·Nazanin NazariDavood Rostamzadeh

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