Journal
NATURE IMMUNOLOGY
Volume 15, Issue 11, Pages 1026-1037Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.3005
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Funding
- Swiss National Science Foundation [310030-124922/1]
- Swiss Federal Institute of Technology Zurich [ETH-34 13-1]
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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-gamma determined the perinatal differentiation and identity of alveolar macrophages (AMs). In contrast, PPAR-gamma 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-gamma conferred a unique signature, including several transcription factors and genes associated with the differentiation and function of AMs. Expression of PPAR-gamma 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-gamma in fetal monocytes.
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