The Gene Signature of Activated M-CSF-Primed Human Monocyte-Derived Macrophages Is IL-10-Dependent

Autor: 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
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Journal of Innate Immunity, Pp 1-14 (2021)
Druh dokumentu: article
ISSN: 1662-811X
1662-8128
DOI: 10.1159/000519305
Popis: 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.
Databáze: Directory of Open Access Journals
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