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10.1159/000519305

http://scihub22266oqcxt.onion/10.1159/000519305
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34670213!9149444!34670213
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suck abstract from ncbi


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pmid34670213      J+Innate+Immun 2022 ; 14 (3): 243-256
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  • The Gene Signature of Activated M-CSF-Primed Human Monocyte-Derived Macrophages Is IL-10-Dependent #MMPMID34670213
  • Cuevas VD; Simon-Fuentes M; Orta-Zavalza E; Samaniego R; Sanchez-Mateos P; Escribese M; Cimas FJ; Bustos M; Perez-Diego M; Ocana A; Dominguez-Soto A; Vega MA; Corbi AL
  • J Innate Immun 2022[]; 14 (3): 243-256 PMID34670213show ga
  • 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-MO). As M-MO display a characteristic cytokine profile after activation (IL10high TNFlow IL23low IL6low), we sought to determine the transcriptional signature of M-MO upon exposure to pathogenic stimuli. Activation of M-MO 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-MO. 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.
  • |*COVID-19[MESH]
  • |*Macrophage Colony-Stimulating Factor/metabolism[MESH]
  • |Cell Differentiation[MESH]
  • |Cells, Cultured[MESH]
  • |Granulocyte-Macrophage Colony-Stimulating Factor/metabolism[MESH]
  • |Humans[MESH]
  • |Interleukin-10/genetics/metabolism[MESH]
  • |Macrophages/metabolism[MESH]


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