Project description:E protein transcription factors specify major immune cell lineages including lymphocytes and interferon-producing plasmacytoid dendritic cells (pDCs). Corepressors of the ETO family can bind to and block transactivation by E proteins, but the physiological role of these interactions remained unclear. We report that ETO protein Mtg16 binds chromatin primarily through the pDC-specific E protein E2-2 in human pDCs. Mtg16-deficient mice showed impaired pDC development and functionality, whereas the specification of the classical dendritic cells (cDCs) was enhanced. The deletion of Mtg16 caused aberrant expression of E protein antagonist Id2 in pDCs. Thus, Mtg16 acts as a cofactor of E2-2 to promote pDC differentiation and restrict cDC development, revealing an unexpected positive role of ETO proteins in E protein activity. Analysis of E2-2 and Mtg16 immunoprecipitated chromatin from CAL-1 cell line.
Project description:E protein transcription factors specify major immune cell lineages including lymphocytes and interferon-producing plasmacytoid dendritic cells (pDCs). Corepressors of the ETO family can bind to and block transactivation by E proteins, but the physiological role of these interactions remained unclear. We report that ETO protein Mtg16 binds chromatin primarily through the pDC-specific E protein E2-2 in human pDCs. Mtg16-deficient mice showed impaired pDC development and functionality, whereas the specification of the classical dendritic cells (cDCs) was enhanced. The deletion of Mtg16 caused aberrant expression of E protein antagonist Id2 in pDCs. Thus, Mtg16 acts as a cofactor of E2-2 to promote pDC differentiation and restrict cDC development, revealing an unexpected positive role of ETO proteins in E protein activity.
Project description:E protein transcription factors specify major immune cell lineages including lymphocytes and interferon-producing plasmacytoid dendritic cells (pDCs). Corepressors of the ETO family can bind to and block transactivation by E proteins, but the physiological role of these interactions remained unclear. We report that ETO protein Mtg16 binds chromatin primarily through the pDC-specific E protein E2-2 in human pDCs. Mtg16-deficient mice showed impaired pDC development and functionality, whereas the specification of the classical dendritic cells (cDCs) was enhanced. The deletion of Mtg16 caused aberrant expression of E protein antagonist Id2 in pDCs. Thus, Mtg16 acts as a cofactor of E2-2 to promote pDC differentiation and restrict cDC development, revealing an unexpected positive role of ETO proteins in E protein activity. pDC from BM of WT and mtg16-KO mice were negatively selected (lin-CD19, Tcrb, Ter119, NK1.1) and sorted as CD11c+Bst2+ population directly in Trizol. RNA was prepared and deposited for microarray processing.
Project description:E protein transcription factors specify major immune cell lineages including lymphocytes and interferon-producing plasmacytoid dendritic cells (pDCs). Corepressors of the ETO family can bind to and block transactivation by E proteins, but the physiological role of these interactions remained unclear. We report that ETO protein Mtg16 binds chromatin primarily through the pDC-specific E protein E2-2 in human pDCs. Mtg16-deficient mice showed impaired pDC development and functionality, whereas the specification of the classical dendritic cells (cDCs) was enhanced. The deletion of Mtg16 caused aberrant expression of E protein antagonist Id2 in pDCs. Thus, Mtg16 acts as a cofactor of E2-2 to promote pDC differentiation and restrict cDC development, revealing an unexpected positive role of ETO proteins in E protein activity.
Project description:Analysis of expression profiles of pDCs from wild type and heterozygous E2-2 mice. Results show the control by E2-2 of the expression of pDC-enriched genes. Experiment Overall Design: Duplicates of both wild type and heterozygous pDCs were used
Project description:Low capacity to produce reactive oxygen species (ROS) due to mutations in neutrophil cytosolic factor 1 (NCF1/p47phox) is strongly associated with lupus development both in humans and mouse models. Here, we aim to identify the major mechanisms of the Ncf1-disease association. We found that plasmacytoid dendritic cells (pDCs), the most potent producers of type I IFNs, exacerbate pristane-induced lupus in ROS-defective Ncf1-mutant and human NCF1-339 variant carrying mice. ROS deficiency in mouse models with Ncf1 mutation or human NCF1-339 variant leads to enhanced pDC generation via the TLR7/AKT/mTOR pathway and accumulation at sites of inflammation, resulting in an increased IFNα secretion. The produced IFNα further stimulates the JAK1/STAT1 pathway, which we found is hyperreactive in ROS-deficient pDCs. This, in turn, leads to increased type I IFN signature and enhanced proinflammatory responses. Our discoveries explain the causative effect of dysfunctional Ncf1 and pathogenicity of pDCs in lupus.
Project description:we report that free cholesterol in the endolysosomal membrane regulates the IFN-I response in plasmacytoid dendritic cells (pDCs) by facilitating the release of TLR9 from UNC93B1.
Project description:Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive malignancy assumed to originate from plasmacytoid dendritic cells (pDCs), which affects the skin and bone marrow and sequentially other organ systems. Here, we used Affymetrix OncoScan CNV arrays to characterize somatic copy number variations in 45 BPDCN cases.
Project description:The steady-state gene expression of pDCs of two different mouse strains was analyzed. Splenic plasmacytoid dendritic cells (pDCs) of Siglec-H knock-out mice on C57Bl& background and the Siglec-H expression littermates (+/+) were enriched and sorted by FACS before generating RNA, followed by cDNA generation and sequencing.
Project description:This SuperSeries is composed of the following subset Series: GSE24726: Gene expression profile of mature plasmacytoid dendritic cells (PDC) after the deletion of transcription factor E2-2 GSE24740: Binding targets of transcription factor E2-2 in human plasmacytoid dendritic cells Refer to individual Series
