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论文题目: mTOR Masters Monocyte Development in Bone Marrow by Decreasing the Inhibition of STAT5 on IRF8
论文题目英文:
作者: 赵阳①,沈晓菲①,#纳宁①,储著郎,苏会婷,晁珊珊,施璐,徐亚男,#张连峰*,#石炳毅*,赵勇*
论文出处:
年: 2018
卷: 131
期: 14
页: 1587-1599
联系作者: #张连峰,#石炳毅,赵勇
发表期刊: Blood
ISSN:
第一作者所在部门:
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论文链接: http://www.bloodjournal.org/content/131/14/1587?sso-checked=true
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摘要:

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 the altered cell metabolism and autophagy. Therefore, our work identifies that mTOR is an intrinsic master for monocyte/macrophage development at the early stages through regulating STAT5-IRF8-dependent CD115-expressing pathway. Long-term usage of RPM may cause a defect of myeloid progenitors in bone marrow.

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