The Gene Signature of Activated M-CSF-Primed Human Monocyte-Derived Macrophages Is IL-10-Dependent
During inflammatory responses, monocytes are recruited into inflamed tissues, where they become monocyte-derived macrophages and acquire pro-inflammatory and tissue-damaging effects in response to the surrounding environment. In fact, monocyte-derived macrophage subsets are major pathogenic cells in...
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2021
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oai:doaj.org-article:30319830d80748f6bed2c0a03d01c2982021-11-18T11:08:45ZThe Gene Signature of Activated M-CSF-Primed Human Monocyte-Derived Macrophages Is IL-10-Dependent1662-811X1662-812810.1159/000519305https://doaj.org/article/30319830d80748f6bed2c0a03d01c2982021-10-01T00:00:00Zhttps://www.karger.com/Article/FullText/519305https://doaj.org/toc/1662-811Xhttps://doaj.org/toc/1662-8128During inflammatory responses, monocytes are recruited into inflamed tissues, where they become monocyte-derived macrophages and acquire pro-inflammatory and tissue-damaging effects in response to the surrounding environment. In fact, monocyte-derived macrophage subsets are major pathogenic cells in inflammatory pathologies. Strikingly, the transcriptome of pathogenic monocyte-derived macrophage subsets resembles the gene profile of macrophage colony-stimulating factor (M-CSF)-primed monocyte-derived human macrophages (M-MØ). As M-MØ display a characteristic cytokine profile after activation (IL10high TNFlow IL23low IL6low), we sought to determine the transcriptional signature of M-MØ upon exposure to pathogenic stimuli. Activation of M-MØ led to the acquisition of a distinctive transcriptional profile characterized by the induction of a group of genes (Gene set 1) highly expressed by pathogenic monocyte-derived macrophages in COVID-19 and whose presence in tumor-associated macrophages (TAM) correlates with the expression of macrophage-specific markers (CD163, SPI1) and IL10. Indeed, Gene set 1 expression was primarily dependent on ERK/p38 and STAT3 activation, and transcriptional analysis and neutralization experiments revealed that IL-10 is not only required for the expression of a subset of genes within Gene set 1 but also significantly contributes to the idiosyncratic gene signature of activated M-MØ. Our results indicate that activation of M-CSF-dependent monocyte-derived macrophages induces a distinctive gene expression profile, which is partially dependent on IL-10, and identifies a gene set potentially helpful for macrophage-centered therapeutic strategies.Víctor D. CuevasMiriam Simón-FuentesEmmanuel Orta-ZavalzaRafael SamaniegoPaloma Sánchez-MateosMaría EscribeseFrancisco J. CimasMatilde BustosMario Pérez-DiegoAlberto OcañaÁngeles Domínguez-SotoMiguel A. VegaÁngel L. CorbíKarger Publishersarticlemacrophageinflammationmacrophage polarizationinterleukin-10MedicineRInternal medicineRC31-1245ENJournal of Innate Immunity, Pp 1-14 (2021) |
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macrophage inflammation macrophage polarization interleukin-10 Medicine R Internal medicine RC31-1245 |
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macrophage inflammation macrophage polarization interleukin-10 Medicine R Internal medicine RC31-1245 Víctor D. Cuevas Miriam Simón-Fuentes Emmanuel Orta-Zavalza Rafael Samaniego Paloma Sánchez-Mateos María Escribese Francisco J. Cimas Matilde Bustos Mario Pérez-Diego Alberto Ocaña Ángeles Domínguez-Soto Miguel A. Vega Ángel L. Corbí The Gene Signature of Activated M-CSF-Primed Human Monocyte-Derived Macrophages Is IL-10-Dependent |
description |
During inflammatory responses, monocytes are recruited into inflamed tissues, where they become monocyte-derived macrophages and acquire pro-inflammatory and tissue-damaging effects in response to the surrounding environment. In fact, monocyte-derived macrophage subsets are major pathogenic cells in inflammatory pathologies. Strikingly, the transcriptome of pathogenic monocyte-derived macrophage subsets resembles the gene profile of macrophage colony-stimulating factor (M-CSF)-primed monocyte-derived human macrophages (M-MØ). As M-MØ display a characteristic cytokine profile after activation (IL10high TNFlow IL23low IL6low), we sought to determine the transcriptional signature of M-MØ upon exposure to pathogenic stimuli. Activation of M-MØ led to the acquisition of a distinctive transcriptional profile characterized by the induction of a group of genes (Gene set 1) highly expressed by pathogenic monocyte-derived macrophages in COVID-19 and whose presence in tumor-associated macrophages (TAM) correlates with the expression of macrophage-specific markers (CD163, SPI1) and IL10. Indeed, Gene set 1 expression was primarily dependent on ERK/p38 and STAT3 activation, and transcriptional analysis and neutralization experiments revealed that IL-10 is not only required for the expression of a subset of genes within Gene set 1 but also significantly contributes to the idiosyncratic gene signature of activated M-MØ. Our results indicate that activation of M-CSF-dependent monocyte-derived macrophages induces a distinctive gene expression profile, which is partially dependent on IL-10, and identifies a gene set potentially helpful for macrophage-centered therapeutic strategies. |
format |
article |
author |
Víctor D. Cuevas Miriam Simón-Fuentes Emmanuel Orta-Zavalza Rafael Samaniego Paloma Sánchez-Mateos María Escribese Francisco J. Cimas Matilde Bustos Mario Pérez-Diego Alberto Ocaña Ángeles Domínguez-Soto Miguel A. Vega Ángel L. Corbí |
author_facet |
Víctor D. Cuevas Miriam Simón-Fuentes Emmanuel Orta-Zavalza Rafael Samaniego Paloma Sánchez-Mateos María Escribese Francisco J. Cimas Matilde Bustos Mario Pérez-Diego Alberto Ocaña Ángeles Domínguez-Soto Miguel A. Vega Ángel L. Corbí |
author_sort |
Víctor D. Cuevas |
title |
The Gene Signature of Activated M-CSF-Primed Human Monocyte-Derived Macrophages Is IL-10-Dependent |
title_short |
The Gene Signature of Activated M-CSF-Primed Human Monocyte-Derived Macrophages Is IL-10-Dependent |
title_full |
The Gene Signature of Activated M-CSF-Primed Human Monocyte-Derived Macrophages Is IL-10-Dependent |
title_fullStr |
The Gene Signature of Activated M-CSF-Primed Human Monocyte-Derived Macrophages Is IL-10-Dependent |
title_full_unstemmed |
The Gene Signature of Activated M-CSF-Primed Human Monocyte-Derived Macrophages Is IL-10-Dependent |
title_sort |
gene signature of activated m-csf-primed human monocyte-derived macrophages is il-10-dependent |
publisher |
Karger Publishers |
publishDate |
2021 |
url |
https://doaj.org/article/30319830d80748f6bed2c0a03d01c298 |
work_keys_str_mv |
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