Alveolar macrophages (AMs) derive from fetal liver monocytes, which colonize the lung during embryonic development and give rise to fully mature AMs perinatally. AM differentiation requires granulocyte macrophage colony-stimulating factor (GM-CSF), but whether additional factors are involved in AM regulation is not known. Here we report that AMs, in contrast to most other tissue macrophages, were also dependent on transforming growth factor-β receptor (TGF-βR) signaling. Conditional deletion of TGF-βR in mice at different time points halted the development and differentiation of AMs. In adult mice, TGF-β was also critical for AM homeostasis. The source of TGF-β was AMs themselves, indicative of an autocrine loop that promotes AM self-maintenance. Mechanistically, TGF-βR signaling resulted in upregulation of PPAR-γ, a signature transcription factor essential for the development of AMs. These findings reveal an additional layer of complexity regarding the guidance cues, which govern the genesis, maturation, and survival of AMs.

肺泡巨噬细胞（AMs）来源于胎儿肝单核细胞，它们在胚胎发育过程中定植在肺部，并在围产期产生完全成熟的AMs。AM分化需要粒细胞巨噬细胞集落刺激因子（GM-CSF），但尚不清楚AM调节是否涉及其他因子。在这里，我们报道，与大多数其他组织巨噬细胞相比，增效剂也依赖于转化生长因子-β受体（TGF-βR）信号传导。在不同时间点小鼠中TGF-βR的条件性缺失阻止了AMs的发育和分化。在成年小鼠中，TGF-β对AM稳态也很关键。TGF-β的来源是AMs本身，这表明可促进AM自我维持的自分泌循环。从机制上讲，TGF-βR信号传导导致PPAR-γ的上调，对AM的发展必不可少的签名转录因子。这些发现揭示了有关指导线索的另一层复杂性，指导线索控制着AM的发生，成熟和生存。