E-MTAB-5218
Ontology highlight
ABSTRACT:
PROVIDER: E-MTAB-5218 | ExpressionAtlas | 2016-11-10
REPOSITORIES: ExpressionAtlas
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| E-MTAB-5218-analysis-methods.tsv | Tabular | |||
| E-MTAB-5218-atlasExperimentSummary.Rdata | Rdata | |||
| E-MTAB-5218-configuration.xml | Xml | |||
| E-MTAB-5218-percentile-ranks.tsv | Tabular | |||
| E-MTAB-5218.condensed-sdrf.tsv | Tabular |
Items per page: 5 1 - 5 of 107 |
Similar Datasets
Project description:Molecular profiling of effect of TNFα neutralization in contrast to anti-IL-17A or anti-IL-17F treatment for 28 days in lungs of M. tuberculosis infected C57BL/6 mice. Animals were treated once per week (starting day-1) with anti-mouse IL-17A or IL-17F antibodies (20 mg/kg i.p.), anti-mouse TNFα antibody (10 mg/kg), respective isotype control antibodies. Moreover, infected and non-infected TNFα-deficient mice were also analysed. Gene expression data revealed major changes of inflammatory and immune gene expression signatures 4 weeks post-infection (including host-pathogen interactions, macrophage recruitment, activation and polarization, host-anti-mycobacterial activities, immunomodulatory responses and extracellular matrix metallopeptidases) after TNFα blockade, while IL-17A or IL-17F neutralization elicited only mild changes of few genes without impaired host resistance four weeks after M. tuberculosis infection.
2016-12-02 | E-MTAB-5218 | biostudies-arrayexpress
Project description:Interleukin-17A (IL-17A) is a key mediator of protective immunity to yeast and bacterial infections but also drives the pathogenesis of several autoimmune diseases, such as psoriasis or psoriatic arthritis. Here, we show that the tetra-transmembrane protein CMTM4 is a subunit of the IL-17 receptor (IL-17R). CMTM4 constitutively associated with IL-17R subunit C (IL-17RC) to mediate its stability, posttranslational modification, and plasma membrane localization. Both mouse and human cell lines deficient in CMTM4 were largely unresponsive to IL-17A, due to their inability to assemble the IL-17 receptor signaling complex. Accordingly, CMTM4-deficient mice were largely resistant to experimental psoriasis. Collectively, our data identified CMTM4 as an essential component of the IL-17 receptor and a potential therapeutic target for treating IL-17-mediated autoimmune diseases.
2022-12-02 | PXD036366 | Pride
Project description:IL-17A is a pro-inflammatory cytokine that promotes host defense against infections and contributes to the pathogenesis of chronic inflammatory diseases. Dendritic cells (DC) are antigen-presenting cells responsible for adaptive immune responses. Here, we report that IL-17A induces intense remodeling of lipid metabolism in human monocyte-derived DC, as revealed by microarrays analysis. In particular NR1H3/LXR-a and its target genes were significantly upregulated in response to IL-17A. IL-17A induced accumulation of Oil Red O-positive lipid droplets in DC leading to the generation of lipid-laden DC. A lipidomic study established that all the analyzed lipid species, i.e phospholipids, cholesterol, triglycerides, cholesteryl esters were elevated in IL-17A-treated DC. The increased expression of membrane lipid transporters in IL-17A-treated DC as well as their enhanced ability to uptake the fatty acid Bodipy-FL-C16 suggested that lipid uptake was the main mechanism responsible for lipid accumulation in response to IL-17A. IL-17A-induced lipid laden DC were able to stimulate allogeneic T cell proliferation in vitro as efficiently as untreated DC, indicating that IL-17A-treated DC are potently immunogenic. This study, encompassed in the field of immunometabolism, points out for the first time IL-17A as a modulator of lipid metabolism in DC and provides a rationale to delineate the importance of lipid-laden DC in IL-17A-related inflammatory diseases. We used microarrays analysis to understand the impact of IL-17A on human monocyte-derived human dendritic cells. We found overexpression of many genes involved in lipid metabolism in IL-17A-treated dendritic cells compared to untreated dendritic cells. In particular NR1H3/LXR-a and its target genes were significantly upregulated in response to IL-17A. IL-17A induced accumulation of Oil Red O-positive lipid droplets in DC leading to the generation of lipid-laden DC. A lipidomic study established that all the analyzed lipid species, i.e phospholipids, cholesterol, triglycerides, cholesteryl esters were elevated in IL-17A-treated DC. The increased expression of membrane lipid transporters in IL-17A-treated DC as well as their enhanced ability to uptake the fatty acid Bodipy-FL-C16 suggested that lipid uptake was the main mechanism responsible for lipid accumulation in response to IL-17A. IL-17A-induced lipid laden DC were able to stimulate allogeneic T cell proliferation in vitro as efficiently as untreated DC, indicating that IL-17A-treated DC are potently immunogenic. This study, encompassed in the field of immunometabolism, points out for the first time IL-17A as a modulator of lipid metabolism in DC and provides a rationale to delineate the importance of lipid-laden DC in IL-17A-related inflammatory diseases. RNA was extracted from untreated in vitro-generated DC at day 0 (DC, 4 biological replicates ) or DC cultured for 12 days with IL-17A, in the absence or presence of IFN-g (DC-17 and DC-G17, 5 biological replicates)
2015-03-31 | E-GEOD-53163 | biostudies-arrayexpress
Project description:The objective was to determine the transcriptional effect of IL-17A on primary colonic epithelial cells in various differentiation states in vitro. The three states included 1) stem/progenitor cell spheroids grown in 50% L-WRN media as described in our previous publication (PMID: 24232249), 2) differentiating colonic epithelial spheroids (DM) placed in differentiation media without L-WRN for 24 hours, 3) terminally differentiated colonocyte spheroids placed in differentiation media without L-WRN for 48 hours as described in our previous publication (PMID: 27264604). Each condition was cultured with or without 20ng/ml recombinant mouse IL-17A for the final 24 hours.
2018-04-10 | E-MTAB-6365 | biostudies-arrayexpress
Project description:Background: IL-17A plays a role in the pathology of spondyloarthritis (SpA), as evidenced by the clinical efficacy of IL-17A inhibitors (IL-17Ai). Nevertheless, the exact role of IL-17A in driving synovial inflammation and pathological remodeling remains unknown. In this study, we investigated the molecular pathways affected by IL-17Ai in SpA synovitis to determine whether this response is tissue- and/or treatment-specific. Methods: Synovial biopsies from 12 peripheral SpA (pSpA) patients before and after 12 weeks of IL-17Ai treatment were analyzed by RNA-sequencing and qPCRs. The synovial tissue response to IL-17Ai in 7 psoriatic arthritis (PsA) patients was compared to: open-source gene expression data of skin biopsies from 15 psoriasis (PsO) patients treated with IL-17Ai; and synovial biopsies from 7 PsA patients receiving IL-12p40/IL-23p40 blockade. Results: Compared to baseline, IL-17Ai significantly modulated the expression of 1255 genes (549 upregulated and 706 downregulated, FDR < 0.1) in the synovium at week 12. The downregulated genes were predominantly associated with inflammatory processes and stromal functions. Comprehensive analysis revealed that IL-17Ai-mediated suppression of bone remodeling is independent of its inhibition of inflammatory pathways. While IL-17Ai consistently attenuated inflammation-related pathways in both psoriatic joints and skin, its effect on bone remodeling pathways was specific to the synovium. This distinguishes IL-17Ai from IL-12p40/IL-23p40 inhibitors, which, while mitigating synovial inflammation, did not affect tissue remodeling. Conclusions: Our findings provide new insights into the molecular mechanisms of IL-17A blockade in pSpA, underscoring its unique role in selectively targeting bone-remodeling processes specific to the joints of individuals with SpA.
2025-12-04 | GSE304063 | GEO
Project description:Atherosclerosis is a chronic inflammatory disease. Lesion progression is primarily mediated by cells of the monocyte/macrophage lineage. Interleukin-17A is a pro-inflammatory cytokine, which modulates immune cell trafficking and is involved inflammation in (auto)immune and infectious diseases. But the role of IL-17A still remains controversial. In the current study we investigated effects of IL-17A on advanced murine and human atherosclerosis, the common disease phenotype in clinical care. 26-weeks old apolipoprotein E-deficient (Apoe-/-) mice were fed a standard chow diet and treated either with IL-17A mAb (n=15) or irrelevant immunoglobulin (n=10) for 16 weeks. Furthermore, essential mechanisms of IL-17A in atherogenesis were studied in vitro. Inhibition of IL-17A markedly prevented atherosclerotic lesion progression (P=0.001) by reducing inflammatory burden and cellular infiltration (P=0.01) and improved lesion stability (P=0.01). In vitro experiments showed that IL-17A plays a role in chemoattractance, monocyte adhesion, sensitization of antigen-presenting cells toward pathogen-derived TLR4 ligands. Also, IL-17A induced a unique transcriptome pattern in monocyte-derived macrophages distinct from known macrophage types. Stimulation of human carotid plaque tissue ex vivo with IL-17A induced a pro-inflammatory milieu and up-regulation of molecules expressed by the IL-17A-induced macrophage subtype. We here show for the first time that functional blockade of IL-17A prevents atherosclerotic lesion progression and induces plaque stabilization in advanced lesions in Apoe-/- mice. The underlying mechanisms involve reduced inflammation and distinct effects of IL-17A on monocyte / macrophage lineage. In addition, translational experiments underline the relevance for the human system. Effects of IL-17A on human monocyte-derived macrophages were assessed (n=2 per group).
2014-10-01 | E-GEOD-60824 | biostudies-arrayexpress
Project description:The goal of this study was to elucidate the effects of inflammation on bone metabolism. As we found IL-17A is induced immediately after bone injury and Il17a−/− mice showed delayed healing, we analyzed the effects of IL-17A on mesenchymal cells in the repair tissue. Most of the IL-17RA+ cells were PαS cells. We collected these cells and analyzed their response to IL-17A by RNA sequencing. This analysis will provide a mechanistic insight into the mechanism of how IL-17A promote bone formation in the context of bone fracture healing. PαS cells were harvested from the injury tissue of wild-type mice and cultured with or without IL-17A or BMP-2. RNAs were harvested at day 7.
2016-03-08 | E-GEOD-77172 | biostudies-arrayexpress
Project description:Peripheral infections can result in neuropsychiatric changes in many contexts, including after recurrent Group A Streptococcus (GAS) infections in children. In a mouse model of intranasal GAS inoculation, we have previously demonstrated in vivo that mice lacking Th17 cells, or the key Th17 cytokines interleukin 17A (IL-17A) or granulocyte-macrophage colony-stimulating factor (GM-CSF), have altered microglial responses. As an attempt to determine whether these cytokines have direct effects on microglia, we cultured primary microglia and incubated them with either interferon gamma (IFNg), IL-17A or GM-CSF for 24 hours, then collected RNA for bulk sequencing. Microglia treated with IFNg or GM-CSF displayed striking transcriptional shifts, including upregulation of many inflammatory genes. IL-17A treatment did not have a noticeable effect on the microglial transcriptome, likely due to the in vitro absence of IL-17A receptors, which are expressed by microglia in vivo.
2023-03-14 | GSE221715 | 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:IL-17A and F are critical cytokines in anti-microbial immunity but also contribute to auto-immune pathologies. Recent evidence suggests that they may be differentially produced by T-helper (Th) cells but the underlying mechanisms remain unknown. To address this question, a logical model containing 82 components and 136 regulatory links was developed and calibrated with original flow cytometry data using naive CD4+ T cells in conditions inducing either IL-17A or F. Model analyses led to the identification of the transcription factors NFAT2A, STAT5A and Smad2 as key components explaining the differential expression of IL-17A and IL-17F, with STAT5A controlling IL-17F expression, and an interplay of NFAT2A, STAT5A and Smad2 controlling IL-17A expression.
2021-04-06 | MODEL2101150001 | BioModels