Induction of the nuclear receptor PPAR-γ by the cytokine GM-CSF is critical for the differentiation of fetal monocytes into alveolar macrophages

Nat Immunol. 2014 Nov;15(11):1026-37. doi: 10.1038/ni.3005. Epub 2014 Sep 28.


Tissue-resident macrophages constitute heterogeneous populations with unique functions and distinct gene-expression signatures. While it has been established that they originate mostly from embryonic progenitor cells, the signals that induce a characteristic tissue-specific differentiation program remain unknown. We found that the nuclear receptor PPAR-γ determined the perinatal differentiation and identity of alveolar macrophages (AMs). In contrast, PPAR-γ was dispensable for the development of macrophages located in the peritoneum, liver, brain, heart, kidneys, intestine and fat. Transcriptome analysis of the precursors of AMs from newborn mice showed that PPAR-γ conferred a unique signature, including several transcription factors and genes associated with the differentiation and function of AMs. Expression of PPAR-γ in fetal lung monocytes was dependent on the cytokine GM-CSF. Therefore, GM-CSF has a lung-specific role in the perinatal development of AMs through the induction of PPAR-γ in fetal monocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD11c Antigen / genetics
  • CD11c Antigen / immunology
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology*
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism*
  • Lung / cytology
  • Lung / immunology
  • Macrophages, Alveolar / cytology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Monocytes / cytology*
  • PPAR gamma / biosynthesis*
  • PPAR gamma / genetics


  • CD11c Antigen
  • PPAR gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor