Essential Role of mTORC1 in Self-Renewal of Murine Alveolar Macrophages.
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.
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Related Subject Headings
- TOR Serine-Threonine Kinases
- Real-Time Polymerase Chain Reaction
- Multiprotein Complexes
- Mice, Knockout
- Mice, Inbred C57BL
- Mice
- Mechanistic Target of Rapamycin Complex 1
- Macrophages, Alveolar
- Immunology
- Homeostasis
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- TOR Serine-Threonine Kinases
- Real-Time Polymerase Chain Reaction
- Multiprotein Complexes
- Mice, Knockout
- Mice, Inbred C57BL
- Mice
- Mechanistic Target of Rapamycin Complex 1
- Macrophages, Alveolar
- Immunology
- Homeostasis