The effect of type I IFN treatment on global gene expression in monocytes undergoing maturation
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PROVIDER: PRJNA474812 | ENA |
REPOSITORIES: ENA
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Project description:To analyze the effect of type I IFN on global gene expression in differentiating monocytes, we employed microarray-based gene expression profiling. The MACS-purified mouse BM monocytes were cultured in M-CSF and treated with or without IFN for 60 h. The cells were harvested and isolated RNAs were subjected to microarray analyses.
2018-11-19 | GSE115392 | GEO
Project description:Multiple sclerosis (MS) has been treated with IFN-b for three decades, but the mechanisms underlying its beneficial effects are not well understood. Our study elucidates, in a mouse model of MS, a potential mechanism whereby IFN-b inhibits cooperation between monocytes and T cells, two key immune cell types in MS. We found that IFN-b acts on monocytes to induce secretion of anti-inflammatory molecules, IL-10 and TGF-b, which act on T cells to suppress their production of pro-inflammatory molecules, GM-CSF, TNF, and FASL. Given that these T cell molecules induce proinflammatory features of monocytes, such as IL-1b production, we concluded that IFN-b therapy suppresses cooperation between monocytes and T cells, which otherwise reciprocally amplifies their harmful roles in MS.
2021-05-19 | GSE169670 | GEO
Project description:Compared to primary human monocytes in whole blood cultures, few B cells activated STAT1 in response to stimulation of 2000 IU/ml IFN-beta for 45 minutes. Because activation of STAT1 leads to apoptosis induction, we tested the hypothesis that less pro-apoptotic genes are induced in B cells as compared to monocytes. Manuscript titled: Major differences in the responses of primary human leukocyte subsets to IFN-beta. Abstract: Treatment of cell lines with type I IFNs activates the formation of ISGF3 (STAT1/STAT2/ IRF9), which induces the expression of many genes. To study this response in primary cells, we treated fresh human blood with IFN-beta and used flow cytometry to analyze phosphorylated STATs1, 3 and 5 in CD4+ and CD8+ T cells, B cells, and monocytes. The activation of STAT1 was remarkably different among these leukocyte subsets. In contrast to monocytes, CD4+ and CD8+ T cells, few B cells activated STAT1 in response to IFN-beta, a finding that could not be explained by decreased levels of IFNAR2 or STAT1 or enhanced levels of SOCS1 or relevant protein tyrosine phosphatases in B cells. Micro-array and real-time PCR analyses revealed the induction of STAT1-dependent pro-apoptotic mRNAs in monocytes but not in B cells. These data show that ISGF3 or STAT1 homodimers are not the main activators of gene expression in primary B cells of healthy humans. Notably, in B cells and especially in CD4+ T cells, IFN-beta activated STAT5 in addition to STAT3, with biological effects often opposite from those driven by activated STAT1. These data help to explain why IFN-beta increases the survival of primary human B cells and CD4+ T cells, but enhances the apoptosis of monocytes, and also to understand how leukocyte subsets are differentially affected by endogenous type I IFNs during viral or bacterial infections, and by type I IFN treatment of patients with multiple sclerosis, hepatitis or cancer. Undiluted whole blood of 2 healthy individuals (HI) was used, and either stimulated with IFN-beta or left untreated (control) for 3 hrs. After 3 hrs, both B cells and monocytes were isolated from whole blood of the first healthy individual, and only B cells were isolated from whole blood of the second healthy individual.
2010-10-20 | E-GEOD-23307 | biostudies-arrayexpress
Project description:Macrophages are known to be polarized into inflammatory (M1) and immunoregulatory (M2) cells when they are stimulated by agonists such as IFN-gamma and IL-4, respectively. If circulating monocytes may be polarized in response to T cell signals is often misguidedly deduced from macrophage results. Here the transcriptional responses of human CD14+ monocytes to IFN-gamma and IL-4 were analyzed using whole genome microarrays. A principal component analysis and hierarchical clustering showed that monocyte and macrophage responses were distinct. Monocytes stimulated with IFN-gamma and IL-4 for 6 hours exhibited some features of macrophage polarization. Indeed, when 80 genes considered as M1 and M2 genes were analyzed, we found that M1 genes were modulated in response to IFN-gamma and that M2 genes were modulated in response to IL-4. The M1 polarization of monocytes was transient because only M2 genes were modulated when monocytes were stimulated with IFN-gamma and IL-4 for 18 hours. However, the activation of monocytes by IFN-gamma and IL-4 could not be reduced to M1/M2 polarization status. Indeed, monocytes exhibited early specific signatures composed of 46 and 39 up-regulated genes in response to IFN-gamma and IL-4, respectively, and a late signature common to both molecules that consisted of 57 up-regulated genes. Taken together, these results demonstrated the extreme plasticity of human monocytes and suggested the existence of a core transcriptional termination program. Using early and late signatures might be pertinent to investigate monocyte activation in inflammatory or infectious diseases. Monocytes were stimulated with IFN-gamma (20ng/mL) or IL-4 (20ng/mL) for 6 and 18 hours or culture for 6 and 18 hours without agonist (Unstimulated samples). Monocytes-derived-macrophages (MDM) stimulated with IFN-gamma and IL-4 for 18 hours were used as controls. Each microarray is derived from a single biological sample.
2013-03-15 | E-GEOD-36537 | biostudies-arrayexpress
Project description:Compared to primary human monocytes in whole blood cultures, few B cells activated STAT1 in response to stimulation of 2000 IU/ml IFN-beta for 45 minutes. Because activation of STAT1 leads to apoptosis induction, we tested the hypothesis that less pro-apoptotic genes are induced in B cells as compared to monocytes. Manuscript titled: Major differences in the responses of primary human leukocyte subsets to IFN-beta. Abstract: Treatment of cell lines with type I IFNs activates the formation of ISGF3 (STAT1/STAT2/ IRF9), which induces the expression of many genes. To study this response in primary cells, we treated fresh human blood with IFN-beta and used flow cytometry to analyze phosphorylated STATs1, 3 and 5 in CD4+ and CD8+ T cells, B cells, and monocytes. The activation of STAT1 was remarkably different among these leukocyte subsets. In contrast to monocytes, CD4+ and CD8+ T cells, few B cells activated STAT1 in response to IFN-beta, a finding that could not be explained by decreased levels of IFNAR2 or STAT1 or enhanced levels of SOCS1 or relevant protein tyrosine phosphatases in B cells. Micro-array and real-time PCR analyses revealed the induction of STAT1-dependent pro-apoptotic mRNAs in monocytes but not in B cells. These data show that ISGF3 or STAT1 homodimers are not the main activators of gene expression in primary B cells of healthy humans. Notably, in B cells and especially in CD4+ T cells, IFN-beta activated STAT5 in addition to STAT3, with biological effects often opposite from those driven by activated STAT1. These data help to explain why IFN-beta increases the survival of primary human B cells and CD4+ T cells, but enhances the apoptosis of monocytes, and also to understand how leukocyte subsets are differentially affected by endogenous type I IFNs during viral or bacterial infections, and by type I IFN treatment of patients with multiple sclerosis, hepatitis or cancer.
2010-10-20 | GSE23307 | GEO
Project description:Macrophages are known to be polarized into inflammatory (M1) and immunoregulatory (M2) cells when they are stimulated by agonists such as IFN-gamma and IL-4, respectively. If circulating monocytes may be polarized in response to T cell signals is often misguidedly deduced from macrophage results. Here the transcriptional responses of human CD14+ monocytes to IFN-gamma and IL-4 were analyzed using whole genome microarrays. A principal component analysis and hierarchical clustering showed that monocyte and macrophage responses were distinct. Monocytes stimulated with IFN-gamma and IL-4 for 6 hours exhibited some features of macrophage polarization. Indeed, when 80 genes considered as M1 and M2 genes were analyzed, we found that M1 genes were modulated in response to IFN-gamma and that M2 genes were modulated in response to IL-4. The M1 polarization of monocytes was transient because only M2 genes were modulated when monocytes were stimulated with IFN-gamma and IL-4 for 18 hours. However, the activation of monocytes by IFN-gamma and IL-4 could not be reduced to M1/M2 polarization status. Indeed, monocytes exhibited early specific signatures composed of 46 and 39 up-regulated genes in response to IFN-gamma and IL-4, respectively, and a late signature common to both molecules that consisted of 57 up-regulated genes. Taken together, these results demonstrated the extreme plasticity of human monocytes and suggested the existence of a core transcriptional termination program. Using early and late signatures might be pertinent to investigate monocyte activation in inflammatory or infectious diseases.
2013-03-15 | GSE36537 | GEO
Project description:Type I IFN-inducible gene expression in human blood monocytes primed with Type II IFN. Keywords: repeat sample
2004-09-09 | GSE1740 | GEO
Project description:The ability of dendritic cells (DCs) to activate immunity is linked to their maturation status. In prior studies we have shown that selective antibody-mediated blockade of inhibitory FcgRIIB receptor on human DCs in the presence of activating immunoglobulin (Ig) ligands leads to DC maturation and enhanced immunity to antibody-coated tumor cells. Here we show that Fcg receptor (FcgR) mediated activation of human monocytes and monocyte-derived DCs is associated with a distinct gene expression pattern, including several inflammation associated chemokines as well as type 1 interferon (IFN) response genes including the activation of signal transducer and activator of transcription 1 (STAT1). Experiment Overall Design: To further characterize FcgR mediated enhancement of DC function, we analyzed the gene expression profiles (GEP) of pure populations of monocyte-derived DCs from healthy donors (n=5) using Affymetrix Human Genome U133 Plus2.0 microarrays. Immature DCs cultured in 1% plasma were treated for 24 hours with either anti-FcgRIIB or isotype control antibody. To test whether FcgR mediated DC maturation was distinct from other maturation stimuli, we also compared DCs matured using the inflammatory cytokine cocktail (TNF-a, IL-1b, IL-6 and PGE2) commonly utilized in DC immunotherapy trials. In addition, we also treated Cd14+ monocytes (n=3) with anti-FcgRIIB antibody or isotype control. In order to better characterize the interferon responsive genes in DCs, we treated immature DCs (n=3) with 1000 U/ml of IFN-a2b.
2008-06-15 | E-GEOD-7509 | biostudies-arrayexpress
Project description:Using CITE-sequencing, cell-type specific responses to type-I interferon stimulation were analysed across human CD1c+ dendritic cell and monocyte subsets, showing that IFN-β drives the maturation of DC3 and the acquisition of a unique costimulatory profile characterized by high GITRL expression.
2020-11-01 | GSE157857 | GEO
Project description:The research hypothesis was that the unique expression profile of monocytes in response to Interferon-beta (IFN-β) might be masked by the response profile of the more abundant T cells. The analysis of monocytes response may highlight novel IFN-β functions and pathways that have not been recognized previously. The aim of this study was to characterized the IFN-β transcriptional response in monocytes, a small but influential cell-subset, using gene expression profile and pathway analysis. The expression profiles of purified human monocytes and T cells pulse with IFN-β overnight were compared, and revealed 276 and 42 Differentially Expressed Genes (DEGs) in monocytes and T cells respectively, with only 5 genes common to both sets. Many of the DEGs detected in monocytes were novel with respect to the recognized IFN-β response, and included genes involved in immune-specific activities, communication between cells, regulation of apoptosis, cell migration, and protein translation. Network and pathway analysis of the T cells response revealed the familiar immune pathways, response to virus pathways, and IFN canonical pathway. In monocytes, however, we detected along with known IFN-β-related pathways, such as cell migration also pathways that had not been previously described in the context of IFN-β response, such as the High-Mobility Group Box-1 (HMGB1) signaling pathway. However, most DEGs in monocytes did not cluster to specific networks or canonical pathways. The monocyte-specific DEGs and pathways described herein are beyond the current knowledge regarding the biology of the IFN-β response and the differential response to IFN-β of monocytes versus T cells described emphasizes the importance of cell-specific studies for elucidating the spectrum of cytokine-mediated immunomodulation. Monocytes and T lymphocytes were isolated from 3 healthy volunteers. For each sample the expression profile of untreated cells was compared to the profile of IFN-β treated cells, i.e. 4 samples from each donor (2 cell types, with and without treatment), 12 samples total.
2013-04-22 | E-GEOD-34627 | biostudies-arrayexpress