title: Essential Role of mTORC1 in Self-Renewal of Murine Alveolar Macrophages.
abstract: Alveolar macrophages (AMϕ) have the capacity of local self-renewal through adult life; however, mechanisms that regulate AMϕ 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 AMϕ 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 AMϕ optimal responsiveness to GM-CSF-induced proliferation. Thus, our results demonstrate an essential role of mTORC1 for AMϕ homeostasis by regulating proliferative renewal.
authors.affiliation: School of Laboratory Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.|Division of Allergy and Immunology, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710.
authors.forename: Wenhai
authors.initials: W
authors.lastname: Deng
authors.affiliation: Division of Allergy and Immunology, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710.
authors.forename: Jialong
authors.initials: J
authors.lastname: Yang
authors.affiliation: School of Laboratory Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Xingguang
authors.initials: X
authors.lastname: Lin
authors.affiliation: Division of Allergy and Immunology, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710.
authors.forename: Jinwook
authors.identifier: 0000-0003-3476-7595
authors.initials: J
authors.lastname: Shin
authors.affiliation: School of Laboratory Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; xiaoping.zhong@duke.edu jimingao@yahoo.com.
authors.forename: Jimin
authors.identifier: 0000-0002-3911-043X
authors.initials: J
authors.lastname: Gao
authors.affiliation: Division of Allergy and Immunology, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710; xiaoping.zhong@duke.edu jimingao@yahoo.com.|Department of Immunology, Duke University Medical Center, Durham, NC 27710; and.|Hematologic Malignancies and Cellular Therapies Program, Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710.
authors.forename: Xiao-Ping
authors.identifier: 0000-0002-4619-8783
authors.initials: XP
authors.lastname: Zhong
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000502:physiology; D005434:Flow Cytometry; D006706:Homeostasis / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000166:cytology*; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046912:Multiprotein Complexes / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D058570:TOR Serine-Threonine Kinases / Q000276:immunology*
chemical_list: D046912:Multiprotein Complexes; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases