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• W2143766145 abstract "Abstract Type I IFN differentially regulates the phenotype, function and polarization of particular macrophage populations. M-CSF and GM-CSF are mediators involved in regulating the numbers and function of macrophage lineage populations and have been shown to contribute to macrophage heterogeneity. Type I IFN is an important mediator produced by macrophages and can have profound regulatory effects on their properties. In this study, we compared bone marrow-derived macrophages (BMM) and GM-CSF-induced BMM (GM-BMM) from wild-type and IFNAR1−/− mice to assess the contribution of endogenous type I IFN to the phenotypic differences between BMM and GM-BMM. BMM were capable of higher constitutive IFN-β production, which contributed significantly to their basal transcriptome. Microarray analysis found that of the endogenous type I IFN-regulated genes specific to either BMM or GM-BMM, 488 of these gene alterations were unique to BMM, while only 50 were unique to GM-BMM. Moreover, BMM displayed enhanced basal mRNA levels, relative to GM-BMM, of a number of genes identified as being dependent on type I IFN signaling, including Stat1, Stat2, Irf7, Ccl5, Ccl12, and Cxcl10. As a result of prior type I IFN “priming,” upon LPS stimulation BMM displayed increased activation of the MyD88-independent IRF-3/STAT1 pathways compared with GM-BMM, which correlated with the distinct cytokine/chemokine profiles of the two macrophage subsets. Furthermore, the autocrine type I IFN signaling loop regulated the production of the M1 and M2 signature cytokines, IL-12p70 and IL-10. Collectively, these findings demonstrate that constitutive and LPS-induced type I IFN play significant roles in regulating the differences in phenotype and function between BMM and GM-BMM." @default.
• W2143766145 created "2016-06-24" @default.
• W2143766145 creator A5008427982 @default.
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• W2143766145 creator A5035018866 @default.
• W2143766145 creator A5035045404 @default.
• W2143766145 creator A5056298683 @default.
• W2143766145 date "2009-04-30" @default.
• W2143766145 modified "2023-10-18" @default.
• W2143766145 title "GM-CSF- and M-CSF-dependent macrophage phenotypes display differential dependence on Type I interferon signaling" @default.
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• W2143766145 doi "https://doi.org/10.1189/jlb.1108702" @default.
• W2143766145 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19406830" @default.
• W2143766145 hasPublicationYear "2009" @default.
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