Genome-wide expression analysis of a human pDC cell line
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PROVIDER: PRJNA113257 | ENA |
REPOSITORIES: ENA
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Project description:Analysis of expression profiles of human pDC cell line (CAL1) compared to an immature T cell line (MOLT4) Keywords: Genome-wide expression analysis
2008-10-02 | GSE12507 | GEO
Project description:Analysis of expression profiles of human pDC cell line (CAL1) compared to an immature T cell line (MOLT4) Experiment Overall Design: Duplicates of both CAL1 and MOLT4 cells used
2008-10-26 | E-GEOD-12507 | biostudies-arrayexpress
Project description:Type I interferons (IFN) are crucial mediators of human innate and adaptive immunity and are massively produced from plasmacytoid dendritic cells (pDC). IRF7 is a critical regulator of type I IFN production when pathogens are detected by TLR7/9 in pDC. However, hyperactivation of pDC can cause life-threatening autoimmune diseases. To avoid the deleterious effects of aberrant pDC activation, tight regulation of IRF7 is required. Nonetheless, the detailed mechanisms of how IRF7 transcription is regulated in pDC are still elusive. To this end, we identified the global gene expression changes after stimulation of human primary pDC with the TLR9 agonist CpGB. We identified that the transcription factor MYC is prominently upregulated upon CpGB engagement in pDC. Moreover, when we knocked down MYC in the pDC-like cell line GEN2.2, production of interferon-stimulated genes (ISGs) was dramatically increased and was further enhanced by CpGB. Interestingly, MYC is shown to be recruited to the IRF7 promoter region through interaction with NCOR2/HDAC3 for its repression, and HDAC3 inhibition enhanced IRF7 expression and IFNβ production. Interestingly, activation of TLR9-mediated NF-kB and MAPK and nuclear translocation of IRF7 were greatly enhanced by MYC depletion. Pharmaceutical inhibition of MYC recovered IRF7 expression, further confirming the negative role of MYC in the antiviral response by pDC. Furthermore, the inverse correlation of MYC and IRF7 was validated in psoriasis skin sample datasets. Therefore, our results identify the novel immunomodulatory role of MYC in human pDC and may add to our understanding of aberrant pDC function in autoimmune diseases.
2018-06-01 | GSE70277 | GEO
Project description:Human rhinoviruses (HRV) are usually innocuous viruses; however, they can trigger serious consequences in certain individuals, especially in the setting of deficient interferon (IFN) synthesis. Plasmacytoid dendritic cells (pDC) are key IFN producing cells, though we know little about the mechanisms by which pDC regulate HRV-induced immune responses. Herein we used gene expression microarrays to examine HRV-induced mRNA in blood mononuclear cells from healthy people, in combination with pDC depletion to assess whether observed expression patterns were pDC dependent. As expected, pDC depletion led to a major reduction in HRV-induced IFN-α release, and this was associated with profound differences in gene expression between intact PBMC and pDC depleted PBMC. pDC depletion led to major changes in upstream regulators, with 70-80% of the HRV activated genes appearing to be pDC dependent. PCR validation experiments confirmed changes seen in the microarrays, specifically the extent to which the following differentially expressed genes were highly pDC dependent: the transcription factor IRF7, both IL-27 chains (IL-27 and EBI3), the alpha chain of the IL-15 receptor (IL-15RA) and the IFN stimulated gene IFI27. IL-6, IFN-γ and IL-27 protein synthesis were also highly pDC dependent. Supplementing pDC-depleted cultures with either recombinant IFN-γ, IL-15, IL-27 or IL-6 was able to restore the IFN-α response, thereby compensating for the absence of pDC. Though pDC comprise only a minority population of migratory leukocytes, our findings highlight the extent to which these cells are able to exert a profound effect on the immune response to HRV.
2017-06-10 | GSE99858 | GEO
Project description:Type I interferons (IFN) are crucial mediators of human innate and adaptive immunity and are massively produced from plasmacytoid dendritic cells (pDC). IRF7 is a critical regulator of type I IFN production when pathogens are detected by TLR7/9 in pDC. However, hyperactivation of pDC can cause life-threatening autoimmune diseases. To avoid the deleterious effects of aberrant pDC activation, tight regulation of IRF7 is required. Nonetheless, the detailed mechanisms of how IRF7 transcription is regulated in pDC are still elusive. To this end, we identified the global gene expression changes after stimulation of human primary pDC with the TLR9 agonist CpGB. We identified that the transcription factor MYC is prominently upregulated upon CpGB engagement in pDC. Moreover, when we knocked down MYC in the pDC-like cell line GEN2.2, production of interferon-stimulated genes (ISGs) was dramatically increased and was further enhanced by CpGB. Interestingly, MYC is shown to be recruited to the IRF7 promoter region through interaction with NCOR2/HDAC3 for its repression, and HDAC3 inhibition enhanced IRF7 expression and IFNβ production. Interestingly, activation of TLR9-mediated NF-kB and MAPK and nuclear translocation of IRF7 were greatly enhanced by MYC depletion. Pharmaceutical inhibition of MYC recovered IRF7 expression, further confirming the negative role of MYC in the antiviral response by pDC. Furthermore, the inverse correlation of MYC and IRF7 was validated in psoriasis skin sample datasets. Therefore, our results identify the novel immunomodulatory role of MYC in human pDC and may add to our understanding of aberrant pDC function in autoimmune diseases.
2016-11-30 | GSE70276 | GEO
Project description:CpG 1826 binds to Toll-like receptor (TLR)9, whereas influenza virus PR8 activates pDC via TLR7. Differential stimulation of pDCs is expected to result in unique activation mechanism(s) leading to a different phenotypically and functionally matured pDC We used microarrays to detail the global programme of gene expression underlying the maturation process of pDC activated with CpG 1826 and influenza virus PR8. We identified a distinct expression profile of upregulated immunomediators. Keywords: time course
2007-12-13 | GSE7831 | GEO
Project description:Type I interferons (IFN) are crucial mediators of human innate and adaptive immunity and are massively produced from plasmacytoid dendritic cells (pDC). IRF7 is a critical regulator of type I IFN production when pathogens are detected by TLR7/9 in pDC. However, hyperactivation of pDC can cause life-threatening autoimmune diseases. To avoid the deleterious effects of aberrant pDC activation, tight regulation of IRF7 is required. Nonetheless, the detailed mechanisms of how IRF7 transcription is regulated in pDC are still elusive. To this end, we identified the global gene expression changes after stimulation of human primary pDC with the TLR9 agonist CpGB. We identified that the transcription factor MYC is prominently upregulated upon CpGB engagement in pDC. Moreover, when we knocked down MYC in the pDC-like cell line GEN2.2, production of interferon-stimulated genes (ISGs) was dramatically increased and was further enhanced by CpGB. Interestingly, MYC is shown to be recruited to the IRF7 promoter region through interaction with NCOR2/HDAC3 for its repression, and HDAC3 inhibition enhanced IRF7 expression and IFNβ production. Interestingly, activation of TLR9-mediated NF-kB and MAPK and nuclear translocation of IRF7 were greatly enhanced by MYC depletion. Pharmaceutical inhibition of MYC recovered IRF7 expression, further confirming the negative role of MYC in the antiviral response by pDC. Furthermore, the inverse correlation of MYC and IRF7 was validated in psoriasis skin sample datasets. Therefore, our results identify the novel immunomodulatory role of MYC in human pDC and may add to our understanding of aberrant pDC function in autoimmune diseases.
2016-11-30 | GSE70275 | GEO
Project description:mDC and pDC exhibit distinct TLR expression pattern and differ in their responses to various TLR ligands. The goal of this study was to identify genes, that were differentally expressed between mDC and pDC as a means to determine how TLR signaling pathways operate. Suprisingly, expression of TLR-assoociated signaling proteins were found to be present at equivalent levels between mDC and pDC, despite differential expression of TLRs, and thus revealing insight into use of adaptor proteins that function as general regulators of TLR signaling pathways in both cell types. mDC and pDC were sorted from spleens of mice in 2 independent experiments: The first experiment included 2 replicates of pDC that were cultured in medium for 1h prior to RNA extraction and 1 replicate of mDC that were directly processed for RNA extraction after the sort. In a second experiment we obtained 2 more replicates of mDC that were processed for RNA extraction directly after the sort and run on a seperate microarray for gene expression analysis.
2014-01-01 | E-GEOD-50436 | biostudies-arrayexpress
Project description:The interferon-producing plasmacytoid dendritic cells (PDC) share common progenitors with antigen-presenting classical dendritic cells (cDC), yet they possess distinct morphology and molecular features resembling those of lymphocytes. It is unclear whether the unique cell fate of PDC is actively maintained in the steady state. We report that the deletion of transcription factor E2-2 from mature peripheral PDC caused their spontaneous differentiation into cells with cDC properties. This included the loss of PDC markers, increase in MHC class II expression and T cell priming capacity, acquisition of dendritic morphology and induction of cDC signature genes. Genome-wide chromatin immunoprecipitation revealed direct binding of E2-2 to key PDC-specific and lymphoid genes, as well as to certain genes enriched in cDC. Thus, E2-2 actively maintains the cell fate of mature PDC and opposes the “default” cDC fate, in part through direct regulation of lineage-specific gene expression programs. Inducible deletion of E2-2 (Tcf4) has been performed by administering tamoxifen to conditional E2-2flox/flox Rosa26-CreER+ mice or to E2-2flox/flox Rosa26-CreER- control littermates. Four or six days later total splenocytes were isolated, pooled from 2-3 mice and PDC (CD11b- B220+ CD11clow Bst2+) were isolated by sorting. Global gene expression profiles of E2-2-deficient (null) and control (Ctrl) PDC were compared using Affymetrix microarrays (GPL1261).
2010-12-21 | E-GEOD-24726 | biostudies-arrayexpress
Project description:The interferon-producing plasmacytoid dendritic cells (PDC) share common progenitors with antigen-presenting classical dendritic cells (cDC), yet they possess distinct morphology and molecular features resembling those of lymphocytes. It is unclear whether the unique cell fate of PDC is actively maintained in the steady state. We report that the deletion of transcription factor E2-2 from mature peripheral PDC caused their spontaneous differentiation into cells with cDC properties. This included the loss of PDC markers, increase in MHC class II expression and T cell priming capacity, acquisition of dendritic morphology and induction of cDC signature genes. Genome-wide chromatin immunoprecipitation revealed direct binding of E2-2 to key PDC-specific and lymphoid genes, as well as to certain genes enriched in cDC. Thus, E2-2 actively maintains the cell fate of mature PDC and opposes the “default” cDC fate, in part through direct regulation of lineage-specific gene expression programs.
2010-12-21 | GSE24726 | GEO