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Karger AG","issue":"3","license":[{"start":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T00:00:00Z","timestamp":1634688000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T00:00:00Z","timestamp":1634688000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Innate Immun"],"published-print":{"date-parts":[[2022]]},"abstract":"<jats:p>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-M\u00d8). As M-M\u00d8 display a characteristic cytokine profile after activation (IL10&lt;sup&gt;high&lt;\/sup&gt; TNF&lt;sup&gt;low&lt;\/sup&gt; IL23&lt;sup&gt;low&lt;\/sup&gt; IL6&lt;sup&gt;low&lt;\/sup&gt;), we sought to determine the transcriptional signature of M-M\u00d8 upon exposure to pathogenic stimuli. Activation of M-M\u00d8 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 (&lt;i&gt;CD163&lt;\/i&gt;, &lt;i&gt;SPI1&lt;\/i&gt;) and &lt;i&gt;IL10&lt;\/i&gt;. 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-M\u00d8. 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. <\/jats:p>","DOI":"10.1159\/000519305","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T21:02:21Z","timestamp":1634763741000},"page":"243-256","source":"Crossref","is-referenced-by-count":27,"title":["The Gene Signature of Activated M-CSF-Primed Human Monocyte-Derived Macrophages Is IL-10-Dependent"],"prefix":"10.1159","volume":"14","author":[{"given":"V\u00edctor 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