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Title[redir]:
Induction of the nuclear receptor PPAR-γ by the cytokine GM-CSF is critical for the differentiation of fetal monocytes into alveolar macrophages | Nature Immunology
Description:
Details of the ontogeny of alveolar macrophages remain unclear. Kopf and colleagues show that fetal monocytes give rise to alveolar macrophages in a manner dependent on the nuclear receptor PPAR-γ and the cytokine GM-CSF. 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.
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nature portfolio permissions reprints peroxisome proliferator-activated receptor-γ privacy policy specific gene-expression profile open-source system distinct gene-expression signatures advertising gene-expression profiles social media content fate ppar-titioning nuclear receptor ppar-γ nature 391 nature 493 nature 457 nature conditional gene targeting rosa26-stopflox-tdrfp mice43 quantitative real-time pcr controls dectin-1-dependent development stroma-derived interleukin-34 controls author correspondence monocyte-derived alveolar macrophages springerlink instant access survey steady-state tissues yolk sac-derived macrophages molecular health sciences lymphoid specific expression tissue-resident macrophages permissions article schneider cd11ccreppargfl/fl cells compared arrested immature cd11ccreppargfl/fl immature arrested cd11ccreppargfl/fl ppar-γ conferred macrophage populations alveolar macrophage function colony stimulating factors bar graphs display microarray data management ef780–cd45+cd64+autofluorescence+ white adipose tissue privacy article purchase peritoneal macrophage signature alveolar macrophages develop extracellular vesicles derived monocyte inflammatory cytokines tissue-restricted ligand present address
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headline:Induction of the nuclear receptor PPAR-γ by the cytokine GM-CSF is critical for the differentiation of fetal monocytes into alveolar macrophages
description:Details of the ontogeny of alveolar macrophages remain unclear. Kopf and colleagues show that fetal monocytes give rise to alveolar macrophages in a manner dependent on the nuclear receptor PPAR-γ and the cytokine GM-CSF. 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.
datePublished:2014-09-28T00:00:00Z
dateModified:2014-09-28T00:00:00Z
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headline:Induction of the nuclear receptor PPAR-γ by the cytokine GM-CSF is critical for the differentiation of fetal monocytes into alveolar macrophages
description:Details of the ontogeny of alveolar macrophages remain unclear. Kopf and colleagues show that fetal monocytes give rise to alveolar macrophages in a manner dependent on the nuclear receptor PPAR-γ and the cytokine GM-CSF. 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.
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