Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA232810 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:To understand the role of epidermal keratinocytes in immunopathology of skin diseases with predominant T helper (Th) cell responses, we measured the genome-wide transcriptional profile of human keratinocytes in response to IFNgamma, IL-4, IL-17A or IL-22, major cytokines produced by Th1, Th2, Th17 or Th22 cells, respectively. IL-6 was also included in the transcriptional profile analysis because a variety of pro-inflammatory stimuli stimulate human keratinocytes to produce IL-6 that has an autocrine or paracrine role in epidermal immunity. We aimed to discover commonly expressed genes in human keratinocytes in response to pro-inflammatory cytokines, which would be associated with common pathophysiological responses in various skin diseases such as skin permeability barrier disruption or epidermal hyperplasia. Normal human keratinocytes (NHKs) were stimulated with IFNγ, IL-4, IL-6, IL-17A and IL-22 for 24 hours and harvested for total RNA extraction and hybridization on Affymetrix microarrays.
2014-10-02 | E-GEOD-53751 | biostudies-arrayexpress
Project description:To understand the role of epidermal keratinocytes in immunopathology of skin diseases with predominant T helper (Th) cell responses, we measured the genome-wide transcriptional profile of human keratinocytes in response to IFNgamma, IL-4, IL-17A or IL-22, major cytokines produced by Th1, Th2, Th17 or Th22 cells, respectively. IL-6 was also included in the transcriptional profile analysis because a variety of pro-inflammatory stimuli stimulate human keratinocytes to produce IL-6 that has an autocrine or paracrine role in epidermal immunity.
2014-10-02 | GSE53751 | GEO
Project description:In psoriasis lesions, a diverse mixture of cytokines is upregulated which influence each other generating a complex inflammatory situation. Although this is the case, the inhibition of Interleukin-17A (IL-17A) alone showed unprecedented clinical results in patients, indicating that IL-17A is a critical inducer of psoriasis pathogenesis. To elucidate IL-17A-driven keratinocyte-intrinsic signaling pathways, we treated monolayers of normal human epidermal keratinocytes in vitro with a mixture of 6 cytokines (IL-17A, TNF-a, IL-17C, IL-22, IL-36g and IFN-g) involved in psoriasis, to mimic the inflammatory milieu in psoriasis lesions. Microarray and gene set enrichment analysis revealed that this cytokine mixture induced similar gene expression changes with the previous transcriptome studies using psoriasis lesions. Importantly, we identified a set of IL-17A-regulated genes in keratinocytes, which recapitulate typical psoriasis genes exemplified by DEFB4A, S100A7, IL19 and CSF3, based on differences in the expression profiles of cells stimulated with 6 cytokines versus cells stimulated with only 5 cytokines lacking IL-17A. Furthermore a specific IL-17A-induced gene, NFKBIZ, which encodes IkappaB-zeta, a transcriptional regulator for NF-kappaB, was demonstrated to have a significant role for IL-17A-induced gene expression. Thus, we present novel in vitro data from normal human keratinocytes that would help elucidating the IL-17A-driven keratinocyte activation in psoriasis. Cytokine mixture-induced gene expression in primary normal human epidermal keratinocytes (NHEKs) was measured at 24 hours after exposure. NHEKs were exposed to the combination of selected six cytokines (IL-17A: 100 ng/ml, TNF-a: 10 ng/ml, IFN-g: 10 ng/ml, IL-17C: 100 ng/ml, IL-22: 100 ng/ml, IL-36g: 500 ng/ml) , or to the different combinations of five of the six cytokines (in total, 7 different treatments and one untreated control). No replicate experiments were conducted.
2016-03-08 | E-GEOD-77719 | biostudies-arrayexpress
Project description:In psoriasis lesions, a diverse mixture of cytokines is upregulated which influence each other generating a complex inflammatory situation. Although this is the case, the inhibition of Interleukin-17A (IL-17A) alone showed unprecedented clinical results in patients, indicating that IL-17A is a critical inducer of psoriasis pathogenesis. To elucidate IL-17A-driven keratinocyte-intrinsic signaling pathways, we treated monolayers of normal human epidermal keratinocytes in vitro with a mixture of 6 cytokines (IL-17A, TNF-a, IL-17C, IL-22, IL-36g and IFN-g) involved in psoriasis, to mimic the inflammatory milieu in psoriasis lesions. Microarray and gene set enrichment analysis revealed that this cytokine mixture induced similar gene expression changes with the previous transcriptome studies using psoriasis lesions. Importantly, we identified a set of IL-17A-regulated genes in keratinocytes, which recapitulate typical psoriasis genes exemplified by DEFB4A, S100A7, IL19 and CSF3, based on differences in the expression profiles of cells stimulated with 6 cytokines versus cells stimulated with only 5 cytokines lacking IL-17A. Furthermore a specific IL-17A-induced gene, NFKBIZ, which encodes IkappaB-zeta, a transcriptional regulator for NF-kappaB, was demonstrated to have a significant role for IL-17A-induced gene expression. Thus, we present novel in vitro data from normal human keratinocytes that would help elucidating the IL-17A-driven keratinocyte activation in psoriasis.
2016-03-08 | GSE77719 | GEO
Project description:In this study we tested interactions between IL-36 and IL-17A in human keratinocytes. 24 hours of IL-36 stimulation in keratinocytes promoted IL-36, IL-17C, and characteristic psoriasis-related molecule expressions in normal human epidermal keratinocytes in dose-dependent manners as measured by mRNA and protein quantification.
2021-12-31 | GSE160904 | GEO
Project description:To delineate mechanisms for psoriasis pathogenesis driven by the interleukin-17A, proteomic dysregulations were studied in a Human Primary Keratinocyte model system. Label-free quantification was performed and fold-changes were obtained for abundances of proteins in IL-17A treated keratinocytes versus those from IL-17A treated keratinocytes.
Briefly, Human Primary Keratinocytes were isolated and treated with the cytokine IL-17A (50ng/ml) in incomplete media devoid of any growth factors. Tryptic digested and desalted peptide samples were injected in Thermoscientific Q-Exactive Plus instruments through EasyNLC HPLC autosampler. The instruments were set to MS1 resolution of 70000 and MS2 resolution of 17500. The acquisition experiments were optimized to run on 120 min gradients.
The MS spectra were analyzed using the Thermoscientific mass informatics platform Proteome discoverer version 2.2. The common workflows for discovery proteomics were used with Mascot and SequestHT as search engines.
This dataset helped to simulate the IL-17A-driven inflammation in keratinocytes and uncovered many putative druggable targets in the context of psoriasis.
2022-08-11 | MSV000090116 | MassIVE
Project description:In atopic dermatitis (AD), epidermal disease hallmarks are driven by a complex cutaneous inflammatory milieu that varies between patients. How these variable inflammatory signatures translate to patient-specific disease endotypes is poorly understood, which hampers the personalized use of targeted drugs. We here employed primary and immortalized keratinocyte-derived human epidermal equivalents stimulated with T helper (Th)2, -17 and -22 cytokines, to unravel which AD-associated cytokines drive specific epidermal disease hallmarks. Th2 cytokines IL-4 and IL-13 were main inducers of a pro-inflammatory and hyperproliferative response. The presence of IL-17A or IL-22 in the Th2 milieu caused spongiosis, impaired keratinocyte differentiation (loss of FLG, IVL, KRT2) and epidermal barrier defects (altered CLDN1, CLDN4, transepithelial impedance). Transcriptomic analyses revealed upregulation of proliferation genes by Th2 cytokines, and activation of different immune pathways upon Th2 cytokines alone and combination of Th2 and Th17/22 cytokines. Downregulation of epidermis development was most apparent upon combined exposure to Th2 cytokines and IL-22. Single-cell spatial transcriptomics showed expansion of keratinocytes expressing high level of proliferation genes in all epidermal layers, and downregulation of terminal differentiation genes in the upper epidermal layers. Our in vitro AD model using Th2 + IL-22 showed the highest transcriptome resemblance with in vivo AD lesional epidermis and we identified IL-22 specific alteration of epidermis development by lipid mediators like ACER1 and AKR1C3. Finally, we revealed that Aryl Hydrocarbon Receptor (AHR) ligands partially restored the barrier defects caused by Th2 and IL-22, whereas combination of AHR ligand Tapinarof with Janus Kinase (JAK) inhibitor I had an even greater restoring effect. Thus, specific combinations of cytokines upregulated in AD skin drive differential disease hallmarks highlighting the importance of personalized medicine and the need for prediction models in the targeted treatment of AD patients.
2025-06-24 | GSE282371 | GEO
Project description:Transcriptional profile of human epidermal keratinocytes in response to formaldehyde
| PRJNA307346 | ENA
Project description:Transcriptomic Analysis of Human Epidermal Keratinocytes Stimulated with TWEAK, TNF and IL-17A
| PRJNA718582 | ENA