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

• DOI: 10.1038/ni.3005
• Publication Date: 2014-09-29T03:30:53Z
• Authors: Christoph Schneider; Samuel P Nobs; Michael Kurrer; Hubert Rehrauer; Christoph Thiele; Manfred Kopf
• Keywords: Mice, Knockout; 0301 basic medicine; 2403 Immunology; Gene Expression Profiling; Immunology; Granulocyte-Macrophage Colony-Stimulating Factor; 610 Medicine & health; 10071 Functional Genomics Center Zurich; Cell Differentiation; Monocytes; CD11c Antigen; Mice, Inbred C57BL; PPAR gamma; Mice; 03 medical and health sciences; Gene Expression Regulation; Macrophages, Alveolar; 2723 Immunology and Allergy; 570 Life sciences; biology; Animals; Lung

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.