研究发现，肺泡巨噬细胞(AMs)的发育与分化不仅依赖GM-CSF，还必须通过TGF-β受体信号途径。TGF-β在胚胎期和成年期都对AMs的生成和稳态至关重要，且AMs自身产生TGF-β形成自我维持的反馈环。关键转录因子PPAR-α的上调揭示了这一复杂过程。这些发现揭示了AMs生成、成熟和生存的额外指导线索。
摘要：
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- receptor (TGF-R) signaling. Conditional deletion of TGF-R in mice at different time points halted the development and differentiation of AMs. In adult mice, TGF- was also critical for AM homeostasis. The source of TGF- was AMs themselves, indicative of an autocrine loop that promotes AM self-maintenance. Mechanistically, TGF-R signaling resulted in upregulation of PPAR-, 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. Copyright 2017 Elsevier Inc. All rights reserved.
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