Essential Role of mTORC1 in Self-Renewal of Murine Alveolar Macrophages

被引:37
作者
Deng, Wenhai [1 ,2 ]
Yang, Jialong [2 ]
Lin, Xingguang [1 ]
Shin, Jinwook [2 ]
Gao, Jimin [1 ]
Zhong, Xiao-Ping [2 ,3 ,4 ]
机构
[1] Wenzhou Med Univ, Sch Lab Med, Wenzhou 325035, Zhejiang, Peoples R China
[2] Duke Univ, Med Ctr, Dept Pediat, Div Allergy & Immunol, Box 2644, Durham, NC 27710 USA
[3] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA
[4] Duke Univ, Med Ctr, Duke Canc Inst, Hematol Malignancies & Cellular Therapies Progr, Durham, NC 27710 USA
基金
美国国家卫生研究院;
关键词
COLONY-STIMULATING FACTOR; TUMOR-SUPPRESSOR TSC1; SCLEROSIS COMPLEX 1; GM-CSF; T-CELLS; FETAL MONOCYTES; MAMMALIAN TARGET; SPI-C; DIFFERENTIATION; EFFECTOR;
D O I
10.4049/jimmunol.1501845
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Alveolar macrophages (AM phi) have the capacity of local self-renewal through adult life; however, mechanisms that regulate AM phi self-renewal remain poorly understood. We found that myeloid-specific deletion of Raptor, an essential component of the mammalian/mechanistic target of rapamycin complex (mTORC) 1, resulted in a marked decrease of this population of cells accompanying altered phenotypic features and impaired phagocytosis activity. We demonstrated further that Raptor/mTORC1 deficiency did not affect AM phi development, but compromised its proliferative activity at cell cycle entry in the steady-state as well as in the context of repopulation in irradiation chimeras. Mechanically, mTORC1 confers AM phi optimal responsiveness to GM-CSF- induced proliferation. Thus, our results demonstrate an essential role of mTORC1 for AM phi homeostasis by regulating proliferative renewal.
引用
收藏
页码:492 / 504
页数:13
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