Project description:miRNA expression profiling of human monocyte-derived dendritic cells (moDCs) during maturation. Immature, 4h and 16h LPS-activated moDCs were used.
Project description:miRNA expression profiling of human monocyte-derived dendritic cells (moDCs) during maturation. Immature, 4h and 16h LPS-activated moDCs were used. In this study were analysed 2 biological samples of RNA extracted from 4h-post LPS stimulation moDCs and 2 bfrom 16h-post LPS stimulation. The RNA from 0h-post LPS stimulation were used as reference sample. Were also performed dye-swaps of each biological sample as technical replicates.
Project description:Transcriptome analysis of different populations of human monocyte-derived myeloid cells: Autologous Tolerogenic Dendritic Cells (ATDCs), Monocyte-derived Dendritic Cells (MoDCs) and Monocyte-derived Macrophages (MoMacro)
Project description:A growing body of evidence suggests that inflammatory cytokines have a dualistic role in immunity. In this study, we sought to determine the direct effects IFN-gamma on the differentiation and maturation of human peripheral blood monocyte-derived dendritic cells (moDC). Here, we report that following differentiation of human peripheral-blood monocytes into moDCs with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4, interferon-gamma (IFN-gamma) induces moDC maturation and up-regulates the co-stimulatory markers CD80, CD86, CD95, and MHC Class I, enabling moDCs to effectively generate antigen-specific CD4+ and CD8+ T cell responses for multiple viral and tumor antigens. Interestingly, early exposure of monocytes to high concentrations of IFN-gamma promotes monocyte differentiation into macrophages, despite the presence of GM-CSF and IL-4. However, under low concentrations of IFN-gamma, monocytes continue to differentiate into dendritic cells possessing a unique gene-expression profile, resulting in impairments in subsequent maturation by IFN-gamma and an inability to generate effective antigen-specific CD4+ and CD8+ T cell responses compared to standard moDCs. Monocytes differentiated in the presence of low levels of IFN-gamma downregulate IFN-gamma receptor expression, impairing their response to an inflammatory rechallenge. These findings demonstrate the ability of IFN-gamma to impart differential programs on human moDCs which shape the antigen-specific T cell responses they induce. Timing and intensity of exposure to IFN-gamma can thus determine whether moDCs are tolerogenic or immunostimulating. Human monocyte-derived dendritic cells from 4 healthy donors were differentiated with either GM-CSF and IL-4 (n=4) or GM-CSF, IL-4, and IFN-gamma (n=4). These samples were subsequently hybridized to arrays as 4 biological repeats for each of the two treatment conditions.
Project description:Transcriptome analysis of different populations of human monocyte-derived myeloid cells: Autologous Tolerogenic Dendritic Cells (ATDCs), Monocyte-derived Dendritic Cells (MoDCs) and IL-10 induced dendritic cells (DC-10). GSM 2800573 to GSM 2800584 that were re-analyzed from GSE104438.
Project description:Modulating beta-catenin signaling has attractive therapeutic potential in cancer immunotherapy. Various studies have found that beta-catenin can mediate immune evasion in cancer and promote anti-inflammatory features of antigen-presenting dendritic cells. Multiple small-molecule compounds that inhibit Wnt/beta-catenin signaling are currently in clinical development, but none have reached routine clinical use. Thus, new inhibitors of beta-catenin signaling are desirable. This dataset is the result of an investigation of the effect of small molecular compounds axitinib, ICG-001, nitazoxanide, orlistat, and XAV-939 on the maturation capacity of monocyte-derived dendritic cells (moDC). Treatment of immature moDC was done in combination with the beta-catenin activator 6-BIO. Immature moDCs were obtained by isolating monocytes from PBMC using magnetic beads, which were then differentiated into moDCs using GM-CSF and IL-4 for four days. Compounds were added during the maturation of the moDCs, which was done by adding LPS to the cell culture. After the maturation period of 24 hours, the mature moDCs were collected and processed for RNA sequencing.
Project description:A growing body of evidence suggests that inflammatory cytokines have a dualistic role in immunity. In this study, we sought to determine the direct effects IFN-gamma on the differentiation and maturation of human peripheral blood monocyte-derived dendritic cells (moDC). Here, we report that following differentiation of human peripheral-blood monocytes into moDCs with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4, interferon-gamma (IFN-gamma) induces moDC maturation and up-regulates the co-stimulatory markers CD80, CD86, CD95, and MHC Class I, enabling moDCs to effectively generate antigen-specific CD4+ and CD8+ T cell responses for multiple viral and tumor antigens. Interestingly, early exposure of monocytes to high concentrations of IFN-gamma promotes monocyte differentiation into macrophages, despite the presence of GM-CSF and IL-4. However, under low concentrations of IFN-gamma, monocytes continue to differentiate into dendritic cells possessing a unique gene-expression profile, resulting in impairments in subsequent maturation by IFN-gamma and an inability to generate effective antigen-specific CD4+ and CD8+ T cell responses compared to standard moDCs. Monocytes differentiated in the presence of low levels of IFN-gamma downregulate IFN-gamma receptor expression, impairing their response to an inflammatory rechallenge. These findings demonstrate the ability of IFN-gamma to impart differential programs on human moDCs which shape the antigen-specific T cell responses they induce. Timing and intensity of exposure to IFN-gamma can thus determine whether moDCs are tolerogenic or immunostimulating.
Project description:Monocyte-derived dendritic cells (MoDCs) were obtained from two controls and two Down syndrome patients. A microarray-based transcriptomic analysis was performed on the Clariom D Assay, Human platform (ThermoFisher Scientific).
Project description:The transcription factor β-catenin has been shown to be active in different types of dendritic cells (DCs) with ability to induce tolerogenic or anti-inflammatory features. Monocyte-derived dendritic cells (moDCs) have been widely used in dendritic cell-based cancer therapy, but so far with limited clinical efficacy. It is possible that aberrant differentiation or induction of dual pro- and anti-inflammatory features may decrease the moDCs efficiency to stage the immune attack on cancer cells. Here we show, using moDCs derived from healthy buffycoats, that β-catenin is detectable in both immature and lipopolysaccharide (LPS)-matured DCs.