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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Autores principales: 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
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Publicado: Karger Publishers 2021
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Acceso en línea:https://doaj.org/article/30319830d80748f6bed2c0a03d01c298
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spelling 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)
institution DOAJ
collection DOAJ
language EN
topic macrophage
inflammation
macrophage polarization
interleukin-10
Medicine
R
Internal medicine
RC31-1245
spellingShingle 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
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