Successful Clinical Response in Pneumonia Therapy (SCRIPT)
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PROVIDER: PRJNA682249 | ENA |
REPOSITORIES: ENA
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Project description:Successful Clinical Response in Pneumonia Therapy (SCRIPT)
| PRJNA682250 | ENA
Project description:The functional diversification of dendritic cells (DCs) is a key step in establishing protective immune responses. Despite the importance of this lineage diversity, its genetic basis is not fully understood. DC-SCRIPT (Zfp366) is a poorly known transcription factor expressed in conventional DCs (cDCs) and their committed bone marrow progenitors but not in plasmacytoid DCs (pDCs). We show that mice lacking DC-SCRIPT displayed substantially impaired development of IRF8-dependent conventional DC1 (cDC1), while cDC2 differentiated normally. The residual DC-SCRIPT-deficient cDC1s had impaired CD8+ T-cell cross-priming, which could be in part explained by the direct control of DC-SCRIPT on IL-12p40 production. Genome-wide mapping of DC-SCRIPT binding and gene expression analyses revealed a key role for DC-SCRIPT in maintaining cDC1 identity via the direct regulation of cDC1 signature genes, including Irf8. Our study reveals DC-SCRIPT to be a critical component of the gene regulatory program shaping the functional attributes of cDC1s.
2021-02-24 | GSE165138 | GEO
Project description:Rationale: Streptococcus pneumoniae is the most common bacterial cause of community acquired pneumonia. Some clinical trials have demonstrated a beneficial effect of corticosteroid therapy in community acquired pneumonia, but the mechanisms of this benefit remain unclear. Objectives: To investigate the biologic effects of corticosteroids in pneumococcal pneumonia in mice and in patients Methods: We studied lower respiratory tract transcriptomes from an observational cohort of mechanically ventilated patients and from a pneumonia model in mice. We also carried out comprehensive physiologic, biochemical, and histological analyses in mice to identify mechanisms of lung injury in S. pneumoniae with and without adjunctive steroid therapy. Measurement and Main Results: Transcriptomic analysis identified pleiotropic effects of steroid therapy on the lower respiratory tract in critically ill patients with pneumococcal pneumonia, findings that were reproducible in mice. In mice with pneumonia, dexamethasone in combination with ceftriaxone reduced (1) pulmonary edema formation, (2) alveolar protein permeability, (3) proinflammatory cytokine release, (4) histopathology lung injury score, and (5) hypoxemia, but did not increase bacterial burden. Conclusions: In combination with appropriate antibiotics in mice, treatment of pneumococcal pneumonia with steroid therapy reduces hypoxemia, pulmonary edema, lung permeability, and histologic criteria of lung injury, and also altered inflammatory responses at the protein and gene expression level. The concordance of transcriptional data in the mouse model and in patients with pneumococcal pneumonia supports the translational relevance of this work.
2024-06-05 | GSE246398 | GEO
Project description:Breast cancer is one of the most common causes of cancer-related deaths in women. Nuclear receptors (NR) and their regulators are well known for their role in breast cancer. Especially ligands for the type I NRs, Estrogen Receptor (ER) and Progesterone Receptor have growth promoting effects in breast cancer cells. The NR coregulator DC-SCRIPT (ZNF366) has been found to be a strong and independent prognostic marker in ER positive (ESR1) breast cancer patients. DC-SCRIPT modulates the function of multiple NRs and has opposing effects on type I versus type II NRs. It represses the function of the growth promoting type I NRs, whereas it enhances the mainly anti-proliferative type II NRs. In this study we aimed to gain further insight into the functional role of DC-SCRIPT in breast cancer cells. Therefore, the effect of DC-SCRIPT expression on breast cancer cell gene expression was investigated using a novel DC-SCRIPT-inducible MCF7 breast cancer cell line model. In the presence of DC-SCRIPT, multiple cell cycle related genes were differentially expressed, including the tumor suppressor gene CDKN2B.
2015-08-01 | GSE59995 | GEO
Project description:The functional diversification of dendritic cells (DCs) is a key step in establishing protective immune responses. Despite the importance of this lineage diversity, its genetic basis is not fully understood. DC-SCRIPT (Zfp366) is a poorly known transcription factor expressed in conventional DCs (cDCs) and their committed bone marrow progenitors but not in plasmacytoid DCs (pDCs). We show that mice lacking DC-SCRIPT displayed substantially impaired development of IRF8-dependent conventional DC1 (cDC1), while cDC2 differentiated normally. The residual DC-SCRIPT-deficient cDC1s had impaired CD8+ T-cell cross-priming, which could be in part explained by the direct control of DC-SCRIPT on IL-12p40 production. Genome-wide mapping of DC-SCRIPT binding and gene expression analyses revealed a key role for DC-SCRIPT in maintaining cDC1 identity via the direct regulation of cDC1 signature genes, including Irf8. Our study reveals DC-SCRIPT to be a critical component of the gene regulatory program shaping the functional attributes of cDC1s.
2021-02-24 | GSE165125 | GEO
Project description:Idiopathic pulmonary fibrosis (IPF) and non-specific interstitial pneumonia (NSIP) are the 2 most common forms of idiopathic interstitial pneumonia. Response to therapy and prognosis are remarkably different. The clinical-radiographic distinction between IPF and NSIP may be challenging. We sought to investigate the gene expression profile of IPF vs. NSIP We used microarray to identifiy the gene expression profiles in patients with IPF and NSIP, mixed IPF/NSIP histologic pattern and normal controls.
2018-02-06 | GSE110147 | GEO
Project description:Breast cancer is one of the most common causes of cancer-related deaths in women. Nuclear receptors (NR) and their regulators are well known for their role in breast cancer. Especially ligands for the type I NRs, Estrogen Receptor (ER) and Progesterone Receptor have growth promoting effects in breast cancer cells. The NR coregulator DC-SCRIPT (ZNF366) has been found to be a strong and independent prognostic marker in ER positive (ESR1) breast cancer patients. DC-SCRIPT modulates the function of multiple NRs and has opposing effects on type I versus type II NRs. It represses the function of the growth promoting type I NRs, whereas it enhances the mainly anti-proliferative type II NRs. In this study we aimed to gain further insight into the functional role of DC-SCRIPT in breast cancer cells. Therefore, the effect of DC-SCRIPT expression on breast cancer cell gene expression was investigated using a novel DC-SCRIPT-inducible MCF7 breast cancer cell line model. In the presence of DC-SCRIPT, multiple cell cycle related genes were differentially expressed, including the tumor suppressor gene CDKN2B. MCF7EV (empty vector control) and MCF7SC (DC-SCRIPT-inducible) breast cancer cell lines were treated with doxycyline for a total of 68h (to induce DC-SCRIPT expression in MCF7SC clones). After the first 24h, cells were serum starved for 24h to synchronize the cells. Subsequently, cells were released with 10 nM estradiol during the last 20 hours of culturing. Total RNA from two replicate experiments were obtained, and used to compare MCF7EV to MCF7SC clones.
2015-08-01 | E-GEOD-59995 | biostudies-arrayexpress
Project description:The functional diversification of dendritic cells (DCs) is a key step in establishing protective immune responses. Despite the importance of this lineage diversity, its genetic basis is not fully understood. DC-SCRIPT (Zfp366) is a poorly known transcription factor expressed in conventional DCs (cDCs) and their committed bone marrow progenitors but not in plasmacytoid DCs (pDCs). We show that mice lacking DC-SCRIPT displayed substantially impaired development of IRF8-dependent conventional DC1 (cDC1), while cDC2 differentiated normally. The residual DC-SCRIPT-deficient cDC1s had impaired CD8+ T-cell cross-priming, which could be in part explained by the direct control of DC-SCRIPT on IL-12p40 production. Genome-wide mapping of DC-SCRIPT binding and gene expression analyses revealed a key role for DC-SCRIPT in maintaining cDC1 identity via the direct regulation of cDC1 signature genes, including Irf8. Our study reveals DC-SCRIPT to be a critical component of the gene regulatory program shaping the functional attributes of cDC1s. This SuperSeries is composed of the SubSeries listed below.
2021-02-24 | GSE165361 | GEO
Project description:Dendritic cells (DCs) uniquely direct the adaptive immune response towards activation or inhibition, yet little is known how these opposite programs are regulated at the transcriptional level. Here we applied genome-wide approaches to delineate the molecular function of DC-Specific transCRIPT (DC-SCRIPT/ZNF366), an 11 Zn finger-containing transcription factor potentiating DC-function by limiting IL-10 production. Transcriptome analysis identified DC-SCRIPT to affect expression of genes involved in MAPK signaling, and ChIP-Seq analysis showed binding of DC-SCRIPT to GA-rich enhancers nearby genes encoding MAPK Dual-Specificity Phosphatases (DUSPs). Functional studies demonstrated that DC-SCRIPT-knockdown DCs express much less DUSP4 and exhibit increased phosphorylation of all the three major MAPKs (ERK, JNK and p38). Enhanced ERK signaling in DC-SCRIPT-knockdown DCs led to higher production of the immune-inhibitory cytokine IL-10, which could be reverted by DUSP4 overexpression. These results delineate the molecular mechanism DC-SCRIPT employs to limit IL-10 production in DCs, thereby fine-tuning these professional antigen-presenting cells towards immune activation.
2018-06-19 | GSE78923 | GEO