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GSE65914
Homo sapiens
50 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Rosacea is a common chronic inflammatory skin disease of unknown etiology. Our knowledge about an involvement of the adaptive immune system is very limited. We performed detailed transcriptome analysis, qRT-PCR, and quantitative immunohistochemistry on facial biopsies of rosacea patients, classified according to their clinical subtype. As controls, we used samples from healthy controls. Our study shows significant activation of the immune system in all subtypes of rosacea, characterizing erythematotelangiectatic rosacea (ETR) already as a disease with significant influx of proinflammatory cells. The T cell response is dominated by Th1/Th17-polarized immune cells, as demonstrated by significant upregulation of IFN or IL-17, for example. Chemokine expression patterns support a Th1/Th17 polarization profile of the T cell response. Macrophages and mast cells are increased in all three subtypes of rosacea, while neutrophils reach a maximum in papulopustular rosacea. Our studies also provide evidence for activation of plasma cells with significant antibody production already in ETR, followed by a crescendo pattern towards phymatous rosacea. In sum, Th1/Th17 polarized inflammation and macrophage infiltration is an underestimated hallmark in all subtypes of rosacea. Therapies directly targeting the Th1/Th17 pathway are promising candidates in the future treatment of this skin disease.
Publication Title
Molecular and Morphological Characterization of Inflammatory Infiltrate in Rosacea Reveals Activation of Th1/Th17 Pathways.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The mechanisms of inflammation in acne are not well understood. This study performed in two separate patient populations focused on the activation of adaptive and innate immunity in early inflamed acne. Biopsies were collected from lesional and non-lesional skin of acne patients. Psoriasis patients and healthy volunteers were included in the study for comparison (not included in the records). Using Affymetrix Genechips, we observed significant elevation of the signature cytokines of the Th17 lineage in acne lesions compared to non-lesional skin. The increased expression of IL-17 was confirmed with real-time qPCR (RT-PCR) in two separate patient populations. Cytokines involved in Th17 lineage differentiation (IL-1beta, IL-6, TGF-beta; IL23p19) were remarkably induced at the RNA level. In addition, pro-inflammatory cytokines (IL-8, TNF-), Th1 markers (IL12p40, CXCR3, T-bet, IFN-gamma), T regulatory cell markers (Foxp3, IL-10, TGF-) and antimicrobial peptides (S100A7, S100A9, LNC2, hBD2, hBD3, hCAP18) were induced. Importantly, immunohistochemistry revealed significantly increased numbers of IL-17A positive T cells and CD83 dendritic cells in the acne lesions. In summary our results demonstrate the presence of IL17A positive T cells and the activation of Th17-related cytokines in acne lesions, indicating that the Th17 pathway may play a pivotal role in the disease process, offering new targets of therapy.
Publication Title
IL-17/Th17 pathway is activated in acne lesions.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: First- and third-generation retinoids are the main treatment in acne. Even though efficacious, they lack full selectivity for RAR expressed in the epidermis and infundibulum. Objectives: To characterize the in vitro metabolism and the pharmacology of the novel retinoid trifarotene. Methods: In vitro assays determined efficacy, potency and selectivity on RARs, as well as the activity on the expression of retinoid target genes in human keratinocytes and ex vivo cultured skin. In vivo studies investigated topical comedolytic, anti-inflammatory and depigmenting properties. The trifarotene-induced gene expression profile was investigated in non-lesional skin of acne patients and compared to ex vivo and in vivo models. Finally, the metabolic stability in human keratinocytes and hepatic microsomes was established. Results: Trifarotene is a selective RAR agonist with >20-fold selectivity over RAR and RAR. Trifarotene is active and stable in keratinocytes but rapidly metabolized by human hepatic microsomes, predicting improved safety. In vivo, trifarotene 0.01% applied topically is highly comedolytic and has antiinflammatory and antipigmenting properties. Gene expression studies indicated potent activation of known retinoid-modulated processes (epidermal differentiation, proliferation, stress response, RA metabolism) and novel pathways (proteolysis, transport/skin hydration, cell adhesion) in ex vivo and in vivo models, as well as in human skin after four weeks of topical application of trifarotene 0.005% cream. Conclusion: Based on its RAR selectivity, rapid degradation in human hepatic microsomes and pharmacological properties including potent modulation of epidermal processes, topical treatment with trifarotene is expected to provide strong efficacy combined with a favourable safety profile in acne and ichthyotic disorders.
Publication Title
Nonclinical and human pharmacology of the potent and selective topical retinoic acid receptor-γ agonist trifarotene.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 63 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Regulatory T Cells Orchestrate Similar Immune Evasion of Fetuses and Tumors in Mice.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 33 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Analysis of uterine microenvironment at gene expression level. The hypothesis tested in the present study was that Tregs orchestrated the immune reponse triggered in presence of embryo
Publication Title
Regulatory T Cells Orchestrate Similar Immune Evasion of Fetuses and Tumors in Mice.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
Illumina MouseWG-6 v2.0 expression beadchip
Description
Analysis of B16 tumor microenvironment at gene expression level. The hypothesis tested in the present study was that Tregs orchastrated the immune reponse triggered in presence of tumors
Publication Title
Regulatory T Cells Orchestrate Similar Immune Evasion of Fetuses and Tumors in Mice.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 14 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Analysis of uterine microenvironment at gene expression level. The hypothesis tested in the present study was that Tregs orchestrated the immune reponse triggered in presence of embryo.
Publication Title
Regulatory T Cells Orchestrate Similar Immune Evasion of Fetuses and Tumors in Mice.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip, Illumina MouseWG-6 v2.0 R2 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Epigenetic regulations in the IFNγ signalling pathway: IFNγ-mediated MHC class I upregulation on tumour cells is associated with DNA demethylation of antigen-presenting machinery genes.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip, Illumina MouseWG-6 v2.0 R2 expression beadchip
Description
Reversible MHC class I deficiency on tumour cells is commonly caused by coordinated silencing of antigen-presenting machinery genes and restorable by IFN. Here we describe association of DNA demethylation of selected antigen-presenting machinery gene regulatory regions located in the MHC genomic locus (TAP-1, TAP-2, LMP-2, LMP-7) upon IFN treatment with MHC class I upregulation on tumour cells. Our novel findings demonstrate that IFN acts as an epigenetic modifier upregulating the expression of antigen-presenting machinery genes through DNA demethylation. Our data also cast more light on the role of DNA methylation in tumour cell escape from specific immunity.
Publication Title
Epigenetic regulations in the IFNγ signalling pathway: IFNγ-mediated MHC class I upregulation on tumour cells is associated with DNA demethylation of antigen-presenting machinery genes.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Reversible MHC class I deficiency on tumour cells is commonly caused by coordinated silencing of antigen-presenting machinery genes and restorable by IFN. Here we describe association of DNA demethylation of selected antigen-presenting machinery gene regulatory regions located in the MHC genomic locus (TAP-1, TAP-2, LMP-2, LMP-7) upon IFN treatment with MHC class I upregulation on tumour cells. Our novel findings demonstrate that IFN acts as an epigenetic modifier upregulating the expression of antigen-presenting machinery genes through DNA demethylation. Our data also cast more light on the role of DNA methylation in tumour cell escape from specific immunity.
Publication Title
Epigenetic regulations in the IFNγ signalling pathway: IFNγ-mediated MHC class I upregulation on tumour cells is associated with DNA demethylation of antigen-presenting machinery genes.
Sample Metadata Fields
Specimen part, Cell line
View Samples