Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA341946 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR4174900.fastq.gz | Fastqsanger.gz | |||
| SRR4174910.fastq.gz | Fastqsanger.gz | |||
| SRR4174920.fastq.gz | Fastqsanger.gz | |||
| SRR4174930.fastq.gz | Fastqsanger.gz | |||
| SRR4174901.fastq.gz | Fastqsanger.gz |
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Project description:TRAF3IP2 is a candidate psoriasis susceptibility gene encoding Act1, a ubiquitin ligase that couples the IL-17 receptor to downstream signaling pathways. We investigated the role of Act1 in keratinocyte responses to IL-17 using a tetracycline inducible shRNA targeting TRAF3IP2. Tet exposure for seven days effectively silenced TRAF3IP2 mRNA and Act1 protein, resulting in 761 genes with significant changes in expression (495 down, 266 up, >1.5-fold, p<0.05). Gene Ontology analysis revealed that genes affected by TRAF3IP2 silencing are involved in epidermal differentiation, with early differentiation genes (KRT1, KRT10, DSC1, DSG1) being downregulated and late differentiation genes (SPRR2, SPRR3, LCE3) being upregulated. AP1 binding sites were enriched upstream of genes up-regulated by TRAF3IP2 silencing. Correspondingly, nuclear expression of FosB and Fra1 was increased in TRAF3IP2-silenced cells. Many genes involved in host defense were induced by IL-17 in a TRAF3IP2-dependent fashion. Inflammatory differentiation conditions (serum addition for 4 days postconfluence) markedly amplified these IL-17 responses, while increasing basal levels and TRAF3IP2 silencing-dependent upregulation of late differentiation genes. These findings suggest that TRAF3IP2 may alter both epidermal homeostasis and keratinocyte defense responses to influence psoriasis risk.
2017-08-21 | GSE86451 | GEO
Project description:Our study indicates that lncRNA TRAF3IP2-AS1 serving as a negative regulator of Act1 transcriptional expression and IL-17 signaling pathway activity,recruits SRSF10 to downregulate the transcription of IRF1, which is itself a transcriptional factor for Act1. And the psoriasis-susceptible variant A4165G of TRAF3IP2-AS1 is a gain-of-function mutant that binds more strongly than the wild-type form to SRSF10. It means that TRAF3IP2-AS1 or SRSF10 may be a good target for the treatment of human IL-17-related autoimmune diseases.
2021-01-30 | GSE165781 | GEO
Project description:Chronic autoimmune skin disease characterized by epidermal proliferation with hyper- and para-keratosis. The aberrant background immune response involves helper T-lymphocyte types 1 and 17 and their respective secreted cytokines tumor necrosis factor alpha (TNF) and interleukin 17 (IL-17). These pro-inflammatory cytokines stimulate the activation of keratinocytes, resulting in the release of acute phase cytokines, followed by chronic phase cytokines thus promotes induced hyperplasia of keratinocyte. The pro-differentiative action of fisetin on dual cytokine-induced abnormally proliferating keratinocyte revealed downregulation of psoriasis-associated genes and activation of autophagic genes, as well as normalization of genes involved in keratinocyte terminal differentiation. These result supports the effect of fisetin on improving psoriasis like inflammatory flareups in cultured keratinocyte in vitro.
2023-01-10 | GSE217552 | GEO
Project description:Skin contains poorly understood interdependent cellular networks that facilitate barrier integrity and host immunity, including neurons, and myeloid cells; the latter of which intrinsically express the pleiotropic cytokine IL-33. This work shows selective suppression of IL-33 expression in myeloid cells by activation of itch-sensing neurons bearing the Mas-related G protein receptor A3 (A3). Optogenetic activation of A3 neurons also increased IL-17-expressing γδ T cells, epidermal thickening, and resistance to the human pathogen Schistosoma mansoni, partially through the neuropeptide CGRP. Cell-intrinsic loss of IL-33 in myeloid cells alters chromatin conformation, basally elevates expression and release of IL-17-inducing cytokines (e.g., IL-1β, IL-6), and expands macrophage and cDC2 differentiation, driving both tissue pathology (e.g., epidermal thickening, keratinocyte hyperplasia) and resistance to helminth infection. Our findings suggest a mechanism of cellular cross-talk allowing “itch” neuron activation to alter myeloid composition and cytokine expression patterns for reshaping skin architecture and driving immunity
2024-09-12 | GSE218833 | GEO
Project description:Skin contains poorly understood interdependent cellular networks that facilitate barrier integrity and host immunity, including neurons, and myeloid cells; the latter of which intrinsically express the pleiotropic cytokine IL-33. This work shows selective suppression of IL-33 expression in myeloid cells by activation of itch-sensing neurons bearing the Mas-related G protein receptor A3 (A3). Optogenetic activation of A3 neurons also increased IL-17-expressing γδ T cells, epidermal thickening, and resistance to the human pathogen Schistosoma mansoni, partially through the neuropeptide CGRP. Cell-intrinsic loss of IL-33 in myeloid cells alters chromatin conformation, basally elevates expression and release of IL-17-inducing cytokines (e.g., IL-1β, IL-6), and expands macrophage and cDC2 differentiation, driving both tissue pathology (e.g., epidermal thickening, keratinocyte hyperplasia) and resistance to helminth infection. Our findings suggest a mechanism of cellular cross-talk allowing “itch” neuron activation to alter myeloid composition and cytokine expression patterns for reshaping skin architecture and driving immunity
2024-09-12 | GSE218826 | GEO
Project description:Skin contains poorly understood interdependent cellular networks that facilitate barrier integrity and host immunity, including neurons, and myeloid cells; the latter of which intrinsically express the pleiotropic cytokine IL-33. This work shows selective suppression of IL-33 expression in myeloid cells by activation of itch-sensing neurons bearing the Mas-related G protein receptor A3 (A3). Optogenetic activation of A3 neurons also increased IL-17-expressing γδ T cells, epidermal thickening, and resistance to the human pathogen Schistosoma mansoni, partially through the neuropeptide CGRP. Cell-intrinsic loss of IL-33 in myeloid cells alters chromatin conformation, basally elevates expression and release of IL-17-inducing cytokines (e.g., IL-1β, IL-6), and expands macrophage and cDC2 differentiation, driving both tissue pathology (e.g., epidermal thickening, keratinocyte hyperplasia) and resistance to helminth infection. Our findings suggest a mechanism of cellular cross-talk allowing “itch” neuron activation to alter myeloid composition and cytokine expression patterns for reshaping skin architecture and driving immunity
2024-09-12 | GSE218825 | GEO
Project description:The psoKC (psoriatic keratinocyte) model is represnting the behavour of keratinocytes in the later or chronic stage of psoriasis in response to the main cytokines that constitute the characteristic cytokine milieu, namely IFNg and TNFa (mainly derived by Th1 cells), and IL-17 and IL-22 (mainly derived by Th17 cells).
Additionally, the model explores the role of exogenous PGE2 through the activation of EP4 receptor signaling. The response to the aforementioned stimuli was not only limited to the cell fate decisions of keratinocytes (proliferation, apoptosis or differentiation) but also include their effect on the psoriatic environment with respect to the secretion of ligands and intercellular-acting stimuli.
2022-12-14 | MODEL2109300001 | BioModels
Project description:We sought to provide a comprehensive evaluation of the effects of TNF-α and IL-17 on the keratinocyte gene profile in order to identify genes that might be co-regulated by these cytokines. We then sought to determine how genes that were synergistically activated by both cytokines relate to the psoriasis transcriptome. Here, we identified 160 unique genes that were synergistically up-regulated by IL-17 and TNF-α and 188 unique genes where the two cytokines had at least an additive effect. Among highly up-regulated genes were those involved in neutrophil and lymphocyte chemotaxis, inflammation, and epidermal differentiation. Synergistically up-regulated genes included some of the highest expressed genes in lesional psoriatic skin with an impressive correlation between IL-17/TNF-α induced genes and the psoriasis gene signature. In conclusion, keratinocytes may be key drivers of pathogenetic inflammatory circuits in psoriasis through integrating responses to TNF-α and IL-17. This may explain high efficacy of targeting psoriasis with either anti-TNF-α or agents that block Th17 T-cells/IL-17 and has important implications for the development of new therapeutic agents. Comparison of keratinocyte responses to IL-17, TNF-α (1 ng mL-1 and 10 ng mL-1), and the combination of both cytokines in psoriasis.
2010-11-24 | E-GEOD-24767 | biostudies-arrayexpress
Project description:In psoriasis, inflammation and epidermal hyperplasia are thought to be controlled by T cell-derived cytokines. Evidence now suggests that Th17 and Th22 cells infiltrate psoriasis lesions and by secreting IL-17 and IL-22, respectively, may drive disease-specific gene or cell responses. While studies in model systems indicate that IL-22 has a dominant pathogenic role, there is evolving evidence that IL-17 contributes to features of psoriasis. To more fully understand the role of IL-17 in human disease pathogenesis, we examined psoriatic skin lesions obtained from patients treated with an anti-IL-17 (IL-17 A) monoclonal antibody, LY2439821. In a phase 1, randomized, double-blind, placebo-controlled dose escalation trial, patients with chronic psoriasis were randomized to receive 3 doses of subcutaneous LY2439821 at 5 mg (n=8), 15 mg (n=8), 50 mg (n=8), 150 mg (n=8) or placebo (n=8) at weeks 0, 2 and 4. Repeat biopsies were taken from the same lesional area at baseline, week 2 and 6. At week 6, a PASI75 was observed in 0/8, 2/8, 5/7 and 8/8 patients receiving 5 mg, 15 mg, 50 mg or 150 mg LY2439821 respectively and 0/8 patients receiving placebo. The antibody was well-tolerated. In patients receiving the two highest doses, histological and immunohistochemical analyses of biopsies revealed significant reductions from baseline in keratinocyte proliferation, hyperplasia and epidermal thickness after 2 weeks, as well as reduced infiltration into the dermis and epidermis by T-cells (CD3+) and dendritic cells (CD11c and DC-LAMP). Keratinocyte expression of innate defense proteins, S100A7, S100A8, beta-defensin2 and LL37/cathelicidin was also reduced. By week 6, the skin appeared normal with a reversal of disease defining pathological features. Quantitative RT-PCR revealed decreased expression of interferon gamma (IFN-gamma), IL-22 and IL-17, key cytokines from T cell subsets Th1, Th22 and Th17, respectively. In order to explore the extent to which IL-17 blockade influences an even broader set of inflammatory or psoriatic disease related genes, mRNA levels from skin biopsy samples were evaluated using whole genome microarrays. At week 2, the highest dose of LY2439821 modulated over 1500 genes significantly (>1.5 fold change [FC], p<0.05). Of these, 51 genes were strongly suppressed (>7-fold) including IL-19, lipocalin, amphiregulin, granzyme B, and several chemokines. In a separate analysis, those genes known to be synergistically regulated by both IL-17 and TNF-alpha showed the greatest normalization in expression compared to genes known to be regulated by TNF-alpha alone, IFN-gamma or Interferon alpha. Our data suggest that Th17 cells, through the expression of IL-17, mediate psoriasis pathogenesis, and that neutralization of IL-17 with LY2439821 suppresses signaling through multiple inflammatory circuits by inhibiting expression of cytokines from multiple T cell subsets, as well as chemokines, and antimicrobial proteins from keratinocytes. In a phase 1, randomized, double-blind, placebo-controlled dose escalation trial, patients with chronic psoriasis were randomized to receive 3 doses of subcutaneous LY2439821 at 5 mg (n=8), 15 mg (n=8), 50 mg (n=8), 150 mg (n=8) or placebo (n=8) at weeks 0, 2 and 4. Repeat biopsies were taken from the same lesional area at baseline, week 2 and 6. At week 6, a PASI75 was observed in 0/8, 2/8, 5/7 and 8/8 patients receiving 5 mg, 15 mg, 50 mg or 150 mg LY2439821 respectively and 0/8 patients receiving placebo.
2012-01-31 | E-GEOD-31652 | biostudies-arrayexpress
Project description:These experiments are cytokine stimulations (TNF, IL-17, IFNg) of three keratinocyte lines (HAHA, PAK and BS4). Aim is to determine the metabolic changes induced by these cytokines and correlate with metabolomic profiling of psoriatic, uninvolved and normal skin.
2017-06-19 | ST000697 | MetabolomicsWorkbench