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GSE9946
Homo sapiens
12 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Myeloid dendritic cells (DC) and macrophages play an important role in pathogen sensing and antimicrobial defense. Recently we demonstrated that infection of human DC with intracellular bacterium Listeria monocytogenes (L.monocytogenes) leads to the induction of the immunoinhibitory enzyme indoleamine 2,3-dioxygenase (Popov et al., J Clin Invest, 2006), while in the previous studies L.monocytogenes infection was associated with a rather stimulatory DC phenotype. To clarify this discrepancy we performed comparative microarray analysis of immature mo-DC (immDC), mature stimulatory mo-DC (matDC) and mature inhibitory DC either stimulated with prostaglandin E2 (PGE2-DC) or infected with L.monocytogenes (infDC). Studying infection of human myeloid DC with Listeria monocytogenes, we found out, that infected DC are modified by the pathogen to express multiple inhibitory molecules, including indoleamine 2,3-dioxygenase (IDO), cyclooxygenase-2, interleukin 10 and CD25, which acts on DC as IL-2 scavenger. All these inhibitory molecules, expressed on regulatory DC (DCreg), are strictly TNF-dependent and are in concert suppressing T-cell responses. Moreover, only DCreg can efficiently control the number of intracellular listeria, mostly by IDO-mediated mechanisms and by other factors, remaining to be identified. Analyzing publicly acessible data of transcriptional changes in DC and macrophages, infected by various pathogens and parasites (GEO, GSE360), we noticed that infection of these cells with Mycobacterium tuberculosis causes transcriptional response, comparable with the one caused by listeria in human DC. In fact, granuloma in tuberculosis and listeriosis in vivo are enriched for myeloid DC and macrophages characterized by regulatory phenotype.
Publication Title
Infection of myeloid dendritic cells with Listeria monocytogenes leads to the suppression of T cell function by multiple inhibitory mechanisms.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Effector CD8+ T cells are believed to be terminally differentiated cells having cytotoxic activity and the ability to produce effector cytokines such as INF- and TNF-. We investigated the difference between CXCR1+ and CXCR1- subsets of human effector CD27-CD28-CD8+ T cells. Both subsets similarly expressed cytolytic molecules and exerted substantial cytolytic activity, whereas only the CXCR1- subset had IL-2 productivity and self-proliferative activity and was more resistant to cell death than the CXCR1+ subset. These differences were explained by the specific up-regulation of CAMK4, SPRY2, and IL-7R in the CXCR1- subset and that of pro-apoptotic DAPK1 in the CXCR1+ subset. The IL-2 producers were more frequently found in the IL-7R+ subset of the CXCR1- effector CD8+ T cells than in the IL-7R- subset. IL-7/IL-7R signaling promoted cell survival only in the CXCR1- subset. The present study has highlighted a novel subset of effector CD8+ T cells producing IL-2 and suggests the importance of this subset in the homeostasis of effector CD8+ T cells.
Publication Title
Functional heterogeneity of human effector CD8+ T cells.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The development of T cells has been characterized as taking place over three stages: nave (Tn), central memory (Tcm), and effector memory (Tem) cells.
Publication Title
Polarization diversity of human CD4+ stem cell memory T cells.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
To examine the expressions of HSF1 and SSBP1-mediated gene in control and heat shock conditions, we performed DNA microarray analysis.
Publication Title
Mitochondrial SSBP1 protects cells from proteotoxic stresses by potentiating stress-induced HSF1 transcriptional activity.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 276 Downloadable Samples
Ion Torrent Proton
Description
We collected and compared samples from the cohort consisted of six groups as follows: methotrexate (MTX) monotherapy, combination therapy of MTX and infliximab (IFX), tocilizumab (TCZ) monotherapy, age- and gender-matched HC, and a small number of synovial fluid samples. In order to reduce variation due to the proportion of cells at each developmental stage, we performed transcriptome analysis after sorting CD4+ and CD8+ T cells according to developmental stage. We created a gene list that was significantly expressed in RA T cells, and revealed that pathways such as mTORC1, IL-2-stat5, Cell cycle and interferon-related genes were significantly enriched among them. Overall design: Examination among healthy controls and patients with rheumatoid arthritis, including before and after treatment
Publication Title
Multi-dimensional analysis identified rheumatoid arthritis-driving pathway in human T cell.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Subject
View Samples- Homo sapiens
- 22 Downloadable Samples
- Ion Torrent Proton
Description
We compared whole CD4+ and CD8+ T cells from frozen PBMC samples that were collected before and after treatment initiation of each patient with rheumatoid arthritis. Lists consisting of 858 and 950 differentially expressed genes were created from CD4 and CD8, respectively, and these were used for enrichment analysis. As a result, we found that certain pathways were downregulated after TCZ treatment in both CD4+ and CD8+ T cells, including mechanistic target of rapamycin complex 1 (mTORC1) signaling, the IL-2 pathway, and IFN-related genes. Overall design: Examination between before and after tocilizumab treatment of CD4 and CD8 T cell in rheumatoid arthritis patients
Publication Title
Multi-dimensional analysis identified rheumatoid arthritis-driving pathway in human T cell.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Subject
View Samples- Homo sapiens
- 59 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Biopsies (lymph nodes, ascites or hydrothorax) from 60 patients with cancer of unknown primary origin were analyzed.
Publication Title
A microarray-based gene expression analysis to identify diagnostic biomarkers for unknown primary cancer.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Transcription factor access to regulatory elements is prevented by the nucleosome. Heat shock factor 1 (HSF1) is a winged helix transcription factor that plays roles in control and stressed conditions by gaining access to target elements, but mechanisms of HSF1 access have not been well known in mammalian cells. We show a physical interaction between the wing motif of human HSF1 and replication protein A (RPA), which is involved in DNA metabolism. Depletion of RPA1 abolishes HSF1 access to the promoter of HSP70 in unstressed conditions, and delays its rapid activation in response to heat shock. The HSF1-RPA complex leads preloading of RNA polymerase II and opens chromatin structure by recruiting a histone chaperone FACT. Furthermore, this interaction is required for melanoma cell proliferation. These results provide a mechanistic basis for constitutive HSF1 access to nucleosomal DNA, which is important for both basal and inducible gene expression.
Publication Title
RPA assists HSF1 access to nucleosomal DNA by recruiting histone chaperone FACT.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Tenascin-C (TNC), a cancer-associated extracellular matrix glycoprotein, plays a pivotal role in tumor growth. To identify the genes regulated by TNC during tumor growth, we performed a tumor growth assay, DNA microarray analysis, and quantitative real-time PCR (qRT-PCR). Mouse mammary tumor cells were subcutaneously inoculated into GRS/A (WT) and GRS/A-TgH(Tnc) (TNKO) mice. Tumors in WT mice significantly increased in volume with expressing TNC while tumors in TNKO mice showed hardly detectable levels of TNC. Tumor gene expression profiles between TNKO and WT mice were compared using DNA microarray analysis. We found that 447 genes were up-regulated (TNKO>WT) and 667 genes were down-regulated (TNKO<WT) in the TNKO group. We then classified these genes by Gene Ontology (GO) terms in order to elucidate their biological function. There were three GO terms found related to tumor growth, namely, acute inflammatory response, cell adhesion, and response to wounding. Eighty-three of the genes primarily involved in these GO terms were further validated by qRT-PCR. Eight genes: Tnc, Cxcl2, Cxcl1, Hbegf, Chl1, Cd44, Serpina3n, and F3 were significantly down-regulated relative to the WT. Eighteen genes: Saa3, P2rx7, Ptgs1, Ptger2, Comp, Steap4, Il1rn, Il1b, Ncf1, Mst1, Nfb1, Ctsb, Tnfrsf1a, Tnfrsf1b, Cd24a, Adam17, Mtpn, and Sox4 were significantly up-regulated relative to the WT. These results support our hypothesis that TNC has multi-faceted effects on both the tumor cells and their microenvironment. First, TNC acts on the tumor cells directly by up-regulating genes involved in cancer cell proliferation through the CXCL1/2 and CXCR2 pathway. Second, TNC controls the tumor microenvironment by promoting angiogenesis through the CXCL1/2 and CXCR2 pathway, and by suppressing inflammatory gene expression through a separate pathway.
Publication Title
Comprehensive DNA microarray expression profiles of tumors in tenascin-C-knockout mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 56 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Multi-omics study was conducted to elucidate the crucial molecular mechanisms of primary Sjgrens syndrome (SS) pathology. We generated multiple data set from well-defined patients with SS, which includes whole-blood transcriptomes, serum proteomes and peripheral immunophenotyping. Based on our newly generated data, we performed an extensive bioinformatic investigation. Our integrative analysis identified SS gene signatures (SGS) dysregulated in widespread omics layers, including epigenomes, mRNAs and proteins. SGS predominantly involved the interferon signature and ADAMs substrates. Besides, SGS was significantly overlapped with SS-causing genes indicated by a genome-wide association study and expression trait loci analyses. Combining the molecular signatures with immunophenotypic profiles revealed that cytotoxic CD8 T cells were associated with SGS. Further, we observed the activation of SGS in cytotoxic CD8 T cells isolated from patients with SS. Our multi-omics investigation identified gene signatures deeply associated with SS pathology and showed the involvement of cytotoxic CD8 T cells. These integrative relations across multiple layers will facilitate our understanding of SS at the system level.
Publication Title
Multiomic disease signatures converge to cytotoxic CD8 T cells in primary Sjögren's syndrome.
Sample Metadata Fields
Sex, Age, Specimen part, Disease
View Samples