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

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.