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GSE32407
Homo sapiens
50 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Psoriasis is a chronic, debilitating, immune-mediated inflammatory skin disease. As IFN- is involved in many cellular processes, including activation of T cells and dendritic cells (DCs), antigen processing and presentation, cell adhesion and trafficking, and cytokine and chemokine production, IFN--producing Th1 cells were proposed to be integral to the pathogenesis of psoriasis. Recently, IFN- was shown to enhance IL-23 and IL-1 production by DCs and subsequently induce Th17 cells, important contributors to the inflammatory cascade in psoriasis lesions. To determine if IFN- indeed induces the pathways leading to the development of psoriasis lesions, a single intradermal injection of IFN- was administered to an area of clinically normal, non-lesional skin of psoriasis patients and biopsies were collected 24 hours later. Although there were no visible changes in the skin, IFN- induced molecular and histological features characteristic of psoriasis lesions. IFN- increased a number of differentially expressed genes in the skin, including many chemokines concomitant with an influx of T cells and inflammatory DCs. Furthermore, inflammatory DC products TNF, iNOS, IL-23, and TRAIL were present in IFN--treated skin. Thus, IFN-, which is significantly elevated in non-lesional skin compared to healthy skin, appears to be a key pathogenic cytokine that can induce the inflammatory cascade in psoriasis.
Publication Title
A single intradermal injection of IFN-γ induces an inflammatory state in both non-lesional psoriatic and healthy skin.
Sample Metadata Fields
Disease, Disease stage
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Background: Previous work has identified CD11c+CD1c- dendritic cells (DCs) as the major inflammatory dermal DC population in psoriasis vulgaris and CD1c+ DCs as the resident cutaneous DC population. Objective: To further define molecular differences between these two myeloid dermal DC populations. Methods: Inflammatory and resident DCs were single-cell sorted from psoriasis lesional skin biopsies, and gene array expression profiling was performed. Results were confirmed with RT-PCR, flow cytometry, immunohistochemistry, and double label immunofluorescence. Pooled human keratinocytes were cultured for functional studies. Results: TNF-related apoptosis-inducing ligand (TRAIL), Toll-like receptors (TLRs) 1 and 2, S100A12/EN-RAGE, CD32, and many other inflammatory products were selectively expressed in inflammatory DCs than in resident DCs. Flow cytometry and immunofluorescence confirmed higher protein expression on CD1c- versus CD1c+ DCs. TRAIL receptor, death receptor 4 (DR4), was expressed on basal keratinocytes and blood vessels, and in vitro culture of keratinocytes with rh-TRAIL induced CCL20 leukocyte chemokine. Conclusion: CD11c+CD1c- inflammatory DCs in psoriatic lesional skin express a wide range of inflammatory molecules compared to skin resident CD1c+ DCs. Some molecules made by inflammatory DCs, including TRAIL, could have direct effects on keratinocytes or other skin cell types to promote disease pathogenesis.
Publication Title
Identification of TNF-related apoptosis-inducing ligand and other molecules that distinguish inflammatory from resident dendritic cells in patients with psoriasis.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
We sought to define the cutaneous response at 24 hours following erythemogenic doses of narrow-band UVB (NB-UVB, 312 nm peak) exposure and determine the differences between irradiated and non-irradiated skin.
Publication Title
Gene profiling of narrowband UVB-induced skin injury defines cellular and molecular innate immune responses.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Our group recently described a population of antigen presenting cells that appear to be critical in psoriasis pathogenesis, termed inflammatory myeloid dendritic cells (CD11c+ BDCA1-). Triggering receptor expressed on myeloid cells type-1 (TREM-1) signaling was a major canonical pathway in the published transcriptome of these cells. TREM-1 is a member of the immunoglobulin superfamily, active through the DAP12 signaling pathway, with an unknown ligand. Activation through TREM-1 induces inflammatory cytokines including IL-8, MCP/CCL2 and TNF. We now show that TREM-1 was expressed in the skin of healthy and psoriatic patients, and there was increased soluble TREM-1 in the circulation of psoriasis patients. In psoriasis lesions, TREM-1 was co-localized with dendritic cells as well as CD31+ endothelial cells. TREM-1 expression was reduced with successful NB-UVB, etanercept and anti-IL-17 treatments. An in vitro model of PGN-activated monocytes as inflammatory myeloid DCs was developed to study TREM-1 blockade, and treatment with a TREM-1 blocking chimera decreased allogeneic Th17 activation, as well as IL-17 production. Furthermore, TREM-1 blockade of ex vivo psoriatic dendritic cells in an alloMLR also showed a decrease in IL-17. Together, these data suggest that the TREM-1 signaling pathway offers a novel therapeutic target to prevent the effects of inflammatory myeloid DCs in psoriasis.
Publication Title
TREM-1 as a potential therapeutic target in psoriasis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
To understand the development of new psoriasis lesions, we studied a group of moderate-to-severe psoriasis patients who experienced a relapse after ceasing efalizumab (anti-CD11a, Raptiva, Genentech). There were increased CD3+ T cells, neutrophils, CD11c+ and CD83+ myeloid DCs, but no increase in CD1c+ resident myeloid DCs. In relapsed lesions, there were many CD11c+CD1c-, inflammatory myeloid DCs identified by TNFSF10/TRAIL, TNF, and iNOS. CD11c+ cells in relapsed lesions co-expressed CD14 and CD16 in situ. Efalizumab induced an improvement in many psoriasis genes, and during relapse, the majority of these genes reversed back to a lesional state. Gene Set Enrichment Analysis (GSEA) of the transcriptome of relapsed tissue showed that many of the gene sets known to be present in psoriasis were also highly enriched in relapse. Hence, on ceasing efalizumab, T cells and myeloid cells rapidly enter the skin to cause classic psoriasis.
Publication Title
Post-therapeutic relapse of psoriasis after CD11a blockade is associated with T cells and inflammatory myeloid DCs.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment, Subject, Time
View Samples- Homo sapiens
- 4 Downloadable Samples
IlluminaGenomeAnalyzerII
Description
Regulatory T-cells (Treg) play an essential role in the negative regulation of immune answers by developing an attenuated cytokine response that allows suppressing proliferation and effector function of T-cells (CD4+ Th). The transcription factor FoxP3 is responsible for the regulation of many genes involved in the Treg gene signature. Its ablation leads to severe immune deficiencies in human and mice. Recent developments in sequencing technologies have revolutionized the possibilities to gain insights into transcription factor binding by ChiP-Seq and into transcriptome analysis by mRNA-Seq. We combine FoxP3 ChiP-Seq and mRNA-Seq in order to understand the transcriptional differences between primary human CD4+ T helper and regulatory T-cells, as well as to study the role of FoxP3 in generating those differences. We show, that mRNA-Seq allows analyzing the transcriptomal landscape of T-cells including the expression of specific splice variants at much greater depth than previous approaches, whereas 50% of transcriptional regulation events have not been described before by using diverse array technologies.
Publication Title
Next-generation insights into regulatory T cells: expression profiling and FoxP3 occupancy in Human.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 49 Downloadable Samples
- Illumina HiSeq 2500
Description
We analyzed the genome-wide expression by RNA-seq of a yeast strain that expresses Cas9d and a guideRNA targeted to the GAL10 locus (called +116), which inhibits GAL10 ncRNA expression from the antisense strand. We compared this strain to a strain expressing a scrambled guideRNA. The goal was to examine the effects of ncRNA inhibition and to examine if CRISPR inhibition of gene expression has off-target effects. We find that CRISPR-mediated inhibtion of GAL10 ncRNA only significantly changes expression of transcripts at the GAL1-10 locus, showing that CRISPR is highly specific, and that GAL10 ncRNA only control genes at the GAL locus. Overall design: RNA-seq of 2 strains with CRISPR scrambled and 2 strains with CRISPR +116, the latter of which inhibits GAL10 ncRNA
Publication Title
Single-Molecule Imaging Reveals a Switch between Spurious and Functional ncRNA Transcription.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Dominant negative PPARγ promotes atherosclerosis, vascular dysfunction, and hypertension through distinct effects in endothelium and vascular muscle.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Pharmacological activation of the transcription factor PPAR gamma lowers blood pressure and improves glucose tolerance in humans. In contrast, naturally occurring mutations (e.g., P467L, V290M) in the ligand binding domain of PPAR gamma in humans leads to severe insulin resistance and early-onset hypertension. Experimental evidence, including whole genome expression profiling, suggests that these mutant versions of PPAR gamma act in a dominant negative manner. Because PPAR gamma is expressed in a variety of cell types and tissues, we generated a transgenic mouse model (SP467L) specifically targeting dominant negative PPAR gamma to the vascular smooth muscle cells in order to determine the action of PPAR gamma in the blood vessel independent of its systemic metabolic actions. In the data set provided herein, we examined the gene expression profile in thoracic aorta from SP467L mice and their control littermates using the Affymetrix Mouse Genome 430 2.0 array.
Publication Title
Dominant negative PPARγ promotes atherosclerosis, vascular dysfunction, and hypertension through distinct effects in endothelium and vascular muscle.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Treatment induced senescence (TIS) is a terminal cell cycle arrest program, increasingly recognized as a tumor suppressor mechanism complementing apoptosis in response to standard chemotherapy regimens. In particular cells with blocked apoptotic pathways rely on senescence as the only remaining failsafe mechanism to keep the neoplastic growth in check. However, little is known about biological properties, long-term fate of senescent tumor cells and their impact on the microenvironment.
Publication Title
Opposing roles of NF-κB in anti-cancer treatment outcome unveiled by cross-species investigations.
Sample Metadata Fields
No sample metadata fields
View Samples