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.