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GSE46873
Homo sapiens
11 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Immuno-chemotherapy regimens elicit high response rates in B-cell non-Hodgkin lymphoma but heterogeneity in response duration is observed, with some patients achieving cure and others showing refractory disease or relapse. Using a transcriptome-powered targeted proteomics screen, we discovered a gene regulatory circuit involving the nuclear factor CYCLON which characterizes aggressive disease and resistance to the anti-CD20 monoclonal antibody, Rituximab, in high-risk B-cell lymphoma. CYCLON knockdown was found to inhibit the aggressivity of MYC-overexpressing tumors in mice and to modulate gene expression programs of biological relevance to lymphoma. Furthermore, CYCLON knockdown increased the sensitivity of human lymphoma B cells to Rituximab in vitro and in vivo. Strikingly, this effect could be mimicked by in vitro treatment of lymphoma B cells with a small molecule inhibitor for BET bromodomain proteins (JQ1). In summary, this work has identified CYCLON as a new MYC cooperating factor that drives aggressive tumor growth and Rituximab resistance in lymphoma. This resistance mechanism is amenable to next-generation epigenetic therapy by BET bromodomain inhibition, thereby providing a new combination therapy rationale for high-risk lymphoma.
Publication Title
Identification of a novel BET bromodomain inhibitor-sensitive, gene regulatory circuit that controls Rituximab response and tumour growth in aggressive lymphoid cancers.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Rattus norvegicus
- 8 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
Description
We hypothesize that changes in adrenal gene expression mediate the increased plasma corticosterone and steroidogenesis in rat pups exposed to hypoxia from birth.
Publication Title
Microarray and real-time PCR analysis of adrenal gland gene expression in the 7-day-old rat: effects of hypoxia from birth.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 8 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The long-term effects of neonatal intermittent hypoxia (IH), an accepted model of apnea-induced hypoxia, are unclear. We have previously shown lasting programming effects on the HPA axis in adult rats exposed to neonatal IH. We hypothesized that neonatal rat exposure to IH will subsequently result in a heightened inflammatory state in the adult. Rat pups were exposed to normoxia (control) or six cycles of 5% IH or 10% IH over one hour daily from postnatal day 2 6. Plasma samples from blood obtained at 114 days of age were analyzed by assessing the capacity to induce transcription in a healthy peripheral blood mononuclear cell (PBMC) population and read using a high-density microarray. The analysis of plasma from adult rats previously exposed to neonatal 5% IH vs. 10% IH resulted in 2,579 significantly regulated genes including increased expression of Cxcl1, Cxcl2, Ccl3, Il1a, and Il1b. We conclude that neonatal exposure to intermittent hypoxia elicits a long-lasting programming effect in the adult resulting in an upregulation of inflammatory-related genes.
Publication Title
Intermittent neonatal hypoxia elicits the upregulation of inflammatory-related genes in adult male rats through long-lasting programming effects.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
ChIP-on-chip analysis identifies IL-22 as direct target gene of ectopically expressed FOXP3 transcription factor in human T cells.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The transcription factor (TF) Forkhead Box P3 (FOXP3) is constitutively expressed in high levels in natural occurring CD4+CD25+ regulatory T cells (nTreg) and is not only the most accepted marker for that cell population, but is considered lineage determinative. Chromatin immunoprecipitation (ChIP) of transcription factors in combination with genomic tiling microarray analysis (ChIP-on-Chip) has been shown to be an appropriate tool to identify FOXP3 transcription factor binding sites (TFBS) on a genome-wide scale. In combination with microarray expression analysis the ChIP-on-Chip technique allows to identify direct FOXP3 target genes. This dataset shows expression data of resting and mitogen stimulated (PMA / ionomycin) retrovirally transduced Jurkat T cells either expressing FOXP3(2) (J-FOXP3) or an empty vector control (J-GFP).
Publication Title
ChIP-on-chip analysis identifies IL-22 as direct target gene of ectopically expressed FOXP3 transcription factor in human T cells.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 28 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Background: Influenza A virus (IAV) infections periodically cause substantial morbidity and mortality in the human population. In the lung, the primary targets for IAV replication are type II alveolar epithelial cells (AECII), which are increasingly recognized for their immunological potential. However, our knowledge of the role of AECII in anti-IAV immunity is incomplete and their in vivo response to infection has not been evaluated. To increase our understanding of their role in host-response to IAV-infection, we analyzed transcriptional regulation in primary AECII isolated from infected mice. Results: Microarray analyses of AECII isolated on the first three days following IAV-infection revealed extensive transcriptional regulation. A multitude of differentially expressed transcripts was identified and in comparison to whole-lung tissue revealed a strong contribution of AECII to respiratory anti-IAV responses. Type I interferon played a major role in the detected gene expression profile and functional pathway analyses showed AECII to be highly active in pathogen recognition, cell recruitment and antigen-presentation. Analysis of Toll-like receptor 7 (TLR7) deficient mice indicated AECII to rely on the hosts expression of this innate IAV-sensor to elicit their full response. Importantly, the AECII transcriptional profiles correlated to cell recruitment and type I interferon levels detected in the lungs of infected animals. Conclusions: Ex vivo analysis of primary murine AECII proved as a powerful tool to increase our understanding of AECII biology in infection. Our analysis revealed an exceptionally strong contribution of AECII to local host defenses by integrating signals provided by surrounding cells and direct pathogen recognition.
Publication Title
Alveolar Type II Epithelial Cells Contribute to the Anti-Influenza A Virus Response in the Lung by Integrating Pathogen- and Microenvironment-Derived Signals.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Noncommunicable chronic respiratory diseases (CRDs) such as chronic obstructive pulmonary disease (COPD) and asthma affect hundreds of millions of people and are associated with increasing morbidity and mortality. CRDs are multifactorial disorders and despite different etiologies they commonly manifest in pulmonary structural (airway remodeling, emphysema) and/or functional changes. In this study we used mice intrinsically developing autoimmune-mediated lung inflammation associated with lung pathology and immune imprinting partly comparable to hallmarks of CRD. The so called SPC-HAxTCR-HA transgenic mice (BALB/c genetic background), express a neo-self antigen (influenza A virus hemagglutinin, HA) on lung alveolar epithelial type II cells in the presence of HA-specific CD4+ T cells leading to the establishment of chronic lung inflammation. In order to characterize the inflammatory lung milieu of SPC-HAxTCR-HA mice in comparison to SPC-HA control mice (lacking HA-specific CD4+ T cells), we performed whole lung tissue transcriptional analyses (n = 3 / group). 378 transcripts were found to be differentially expressed in SPC-HAxTCR-HA lungs. 326 of those were up-regulated and 52 were down-regulated compared to SPC-HA control mice.
Publication Title
Chronic lung inflammation primes humoral immunity and augments antipneumococcal resistance.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Here, we report on experiments in double-transgenic mice, in which RFP is expressed in all Foxp3+ Treg cells, whereas Foxp3-dependent GFP expression is exclusively confined to intrathymically induced Foxp3+ Treg cells. This novel molecular genetic tool enabled us to faithfully track and characterize naturally induced Treg cells of intrathymic (RFP+GFP+) and extrathymic (RFP+GFP) origin in otherwise unmanipulated mice.
Publication Title
Fluorochrome-based definition of naturally occurring Foxp3(+) regulatory T cells of intra- and extrathymic origin.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 21 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
The concept of immune regulation/suppression has been well-established. With thymus-derived CD4 CD25 regulatory T (TR) cells, it became clear that a variety of additional peripherally induced TR cells play vital roles in protection from many harmful immune responses including intestinal inflammation. In the present study, we have analyzed in vivo-induced Ag-specific CD4 TR cells with respect to their molecular and functional phenotype. By comparative genomics we could show that these Ag-specific TR cells induced by chronic Ag stimulation in vivo clearly differ in their genetic program from naturally occurring thymus-derived CD4 CD25 TR cells. This distinct population of induced TR cells express neither CD25 nor the TR-associated transcription factor Foxp3. Strikingly, CD25 is not even up-regulated upon stimulation. Despite the lack in Foxp3 expression, these in vivo-induced CD25 TR cells are able to interfere with an Ag-specific CD8 T cell-mediated intestinal inflammation without significant increase in CD25 and Foxp3 expression. Thus, our results demonstrate that in vivo-induced Ag-specific TR cells represent a distinct population of Foxp3 CD25 TR cells with regulatory capacity both in vitro and in vivo.
Publication Title
Chronic antigen stimulation in vivo induces a distinct population of antigen-specific Foxp3 CD25 regulatory T cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Graft-versus-host disease (GvHD) is still one of the major complications following allogeneic stem cell transplantation (SCT) triggered by alloreactive donor T cells. Whereas murine data have clearly shown the beneficial effects of regulatory T cells (Tregs) on the development of GvHD, data from the human system are rare mainly due to low cell numbers of circulating or organ-infiltrating Tregs in lymphopenic patients. Here, we present a comparative analysis of Tregs from patients with and without acute/ chronic GvHD designed as a dynamical approach studying the whole genome profile over the first 6 months after SCT. For this purpose, blood samples were collected monthly for FACS-based isolation of CD4+CD25highCD127low/- Tregs. The Treg transcriptome showed a high stability in the first half year representing the most sensitive time window for tolerance induction. However, the comparison of the Treg transcriptome from patients with and without GvHD uncovered regulated gene transcripts that point to a reduced suppressive function of Tregs with diminished migration capacity to the target organs likely contributing to the development of GvHD. These findings highlight the critical role of human Tregs in the pathophysiology of GvHD and identify novel targets for the manipulation of Tregs to optimize cellular immune intervention strategies.
Publication Title
Human regulatory T cells in allogeneic stem cell transplantation.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Time
View Samples