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

ABSTRACT: Alveolar macrophages (AM?) have the capacity of local self-renewal through adult life; however, mechanisms that regulate AM? 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? 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? optimal responsiveness to GM-CSF-induced proliferation. Thus, our results demonstrate an essential role of mTORC1 for AM? homeostasis by regulating proliferative renewal.

SUBMITTER: Deng W 

PROVIDER: S-EPMC5173435 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature