Skin expression data from psoriasis patients treated with the HSP90 inhibitor RGRN-305
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE193128 | GEO | 2022/01/10
REPOSITORIES: GEO
Similar Datasets
Project description:Skin expression data from psoriasis patients treated with the HSP90 inhibitor RGRN-305
| PRJNA795043 | ENA
Project description:Psoriasis is a common chronic inflammatory skin disease where IκBζ is known to play an important role by mediating IL-17A-driven effects. However, the molecular mechanism by which IL-17A regulates IκBζ expression is not known. We assessed global gene expression my microarray analysis to explore the molecular transformation in blood samples from psoriatic patients during anti-IL-17A (secukinumab) treatment.
2021-03-26 | GSE137220 | GEO
Project description:Psoriasis is a common chronic inflammatory skin disease where IκBζ is known to play an important role by mediating IL-17A-driven effects. However, the molecular mechanism by which IL-17A regulates IκBζ expression is not known. We assessed global gene expression by microarray analysis to explore the molecular transformation in skin samples from psoriatic patients during anti-IL-17A (secukinumab) treatment.
2021-03-26 | GSE137218 | GEO
Project description:Psoriasis is a chronic skin suffering with multiple comorbidities such as psoriatic arthritis and cardiovascular diseases. Increasing evidences have shown the γδ T cells as the sources of IL-17A play critical roles in the psoriatic syndrome. However, there is still lack an effective way to manipulate these pathogenic γδ T cells which were less studied relative to ab T cells. The present study aims to characterize the phenotype of γδ T cells and evaluate the impact of D-mannose (a C-2 epimer of glucose) on γδ T-mediated psoriasis. We found the psoriatic γδ T cells underwent robust proliferation and acquired an IL-17 producing phenotype. The transcriptomic profiles of these skin draining LN γδ T cells had elevated glycolytic features. Importantly, Treatment of D-mannose inhibited γδ T cells and successfully alleviated the local and systematic inflammations induced by imiquimod. The decreased AKT/mTOR/HIF-1a signaling and glycolytic ability may contribute to the suppression of γδ T cells achieved by mannose. Our study deepened the understandings of γδ T cells in psoriasis, meanwhile, promoted D-mannose utilization as a potent clinical application for γδ T cells driven autoimmune diseases.
2022-03-30 | GSE188905 | GEO
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:To investigate treatment effects of secukinumab on clinical signs and psoriatic inflammation markers over 52 weeks in patients with psoriasis.
2023-03-24 | GSE201827 | 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:The immunopathogenesis of psoriasis, a common chronic inflammatory disease of the skin, is still incompletely understood. Here we demonstrate, using a combination of single-cell and spatial-sequencing, that psoriatic fibroblasts, a hitherto unappreciated participant in psoriasis pathogenesis, contribute to the immune network in psoriasis through transition to a pro-inflammatory state characterized by CCL19 and CCL13. Fibroblasts interact with three other main cell-types that are in close proximity: keratinocytes, T cells and myeloid cells, that also interact with each other. In addition, our data demonstrates striking compartmentalization of inflammatory responses in distinct layers of the psoriatic epidermis, including IL-17A responses and autocrine IL-36 autoinflammatory activity within the supraspinous layer. Lastly, our data defined the T cell and myeloid populations involved in psoriasis, including enrichment of CD8+ IL17A expressing T cells, CD16+ dendritic cells, and LAMP3+ dendritic cells. These data provide an unprecedented view of psoriasis pathogenesis, which expands our understanding of the critical cellular players to include inflammatory fibroblasts as well as their cell-cell interactions, defines the spatial compartmentalization of specific inflammatory processes, together a unique resource for future investigations.
2022-09-20 | GSE173706 | GEO
Project description:Psoriasis is a common and chronic inflammatory skin disease complicated by genetic-environmental interactions. Although genomic, transcriptomic and proteomic analyses have been performed to investigate the pathogenesis of psoriasis, the role of metabolites in psoriasis, particularly of lipids, remains unclear. Lipids not only comprise the bulk of the cellular membrane bilayers but also regulate a variety of biological processes, such as cell proliferation, apoptosis, immunity, angiogenesis and inflammation. In this study, an untargeted lipidomics approach was used to study the lipid profiles in psoriasis and identify lipid metabolite signatures for psoriasis through ultra-performance liquid chromatography-quadrupole tandem mass spectrometry. Plasma samples from 90 participants (45 healthy and 45 psoriasis patients) were collected and detected. Statistical analysis was applied to find different features between the disease and control groups. In addition, ELISA was performed to examine differentially-expressed lipids in psoriatic patient plasma. We finally identified several differential expression lipids including LPAs, LysoPCs, PIs, PCs and PAs, among these metabolites, LPAs, LysoPCs and PAs were significantly increased, while PCs and PIs were down-regulated in psoriasis group. We found that elements of the glycerophospholipid metabolism, such as LPAs, LysoPCs, PAs, PIs, and PCs, were significantly altered in the plasma of psoriatic patients. This investigation characterizes the circulating lipids in psoriatic patients and provides novel insights into the pathogenesis of psoriasis.
2017-08-22 | MTBLS408 | MetaboLights
Project description:Psoriasis is a complex chronic inflammatory skin disease, but the exact mechanism underlying its development remains elusive. We found the expression of SHP2 was significantly higher in skin lesions and human peripheral blood mononuclear cells derived from psoriatic patients than those from normal controls. determine whether SHP2 activity affects psoriasis pathogenesis, we treated the murine psoriatic model with SHP099, a potent allosteric inhibitor of SHP2. SHP099 ameliorates the IMQ-induced psoriatic development in mice with unclear molecular mechanism. To address that, single-cell RNA sequencing was performed to explore the role of SHP2 in all cell types in IMQ-induced mouse skin upon SHP099 treatment.
2021-12-16 | GSE165021 | GEO