High-throughput RNA sequencing reveals major alterations of inflammatory molecules involved in pathogenesis of peri- lesional psoriasis after NBUVB treatment
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE179731 | GEO | 2023/03/22
REPOSITORIES: GEO
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Project description:We report the high-throughput profiling of tissue biopsy from psoriasis skin before the start of NB-UVB therapy and after the last treatment session.RNA sequencing (RNA-Seq) was conducted to assay the transcriptomes and identify differentially expressed transcripts enriched in major pathway analysis. Our results support that clinically effective NB-UVB therapy is based on suppression of a broad range of inflammatory signaling pathways, gene expression of inflammatory cytokines, and increased the expression of anti-inflammatory signaling pathways in psoriatic skin.
2023-03-22 | GSE179632 | GEO
Project description:Psoriasis is a common chronic inflammatory and hyperproliferative immune-mediated skin disorder. Narrow-band UVB (NB-UVB) phototherapy is a convenient first-line treatment of psoriasis, though the mechanisms underlying its efficacy have not been completely elucidated. In order to improve our understanding of NB-UVB phototherapy, gene expression profiling was used to characterize gene expression in lesional epidermis from psoriasis patients undergoing NB-UVB phototherapy. Increased expression of melanogenesis pathway genes was observed to be the earliest response. At the end of treatment, genes involved in diverse biological processes were affected, such as pigmentation, cell adhesion, ectodermal development and metabolism. The relationship between gene expression and treatment outcome was further studied using Partial Least Squares Discriminant Analysis (PLS-DA). Gene ontology analysis showed that genes responding to phototherapy and highly correlated to treatment outcome were involved in oxidation reduction, growth and mitochondria organization. In particular SPATA18, a key regulator of mitochondria quality, was found to be significantly downregulated in psoriasis, and its upregulation following phototherapy was required for optimal clinical improvement. Our data suggest that oxidation reduction is a critical event for the resolution of psoriatic plaques. Twelve patients diagnosed with plaque type psoriasis were recruited to the study. NB-UVB irradiation was administered to the whole body two to three times a week. Treatment comprising approximately 24 sessions was given during two to three months. A total of six 4 mm diameter punch biopsies were taken from lesions on each psoriasis patient: two prior to UV treatment (pre-UV), two at the middle stage of UV treatment (after about one month of treatment, mid-UV) and two before the last treatment session (post-UV). Twelve healthy age-, sex- and skin type-matched volunteers were also recruited and two punch biopsies were taken from the buttocks. RNA was extracted from Laser capture microdissected epidermis.
2013-12-23 | E-GEOD-53431 | biostudies-arrayexpress
Project description:Psoriasis is a common chronic inflammatory and hyperproliferative immune-mediated skin disorder. Narrow-band UVB (NB-UVB) phototherapy is a convenient first-line treatment of psoriasis, though the mechanisms underlying its efficacy have not been completely elucidated. In order to improve our understanding of NB-UVB phototherapy, gene expression profiling was used to characterize gene expression in lesional epidermis from psoriasis patients undergoing NB-UVB phototherapy. Increased expression of melanogenesis pathway genes was observed to be the earliest response. At the end of treatment, genes involved in diverse biological processes were affected, such as pigmentation, cell adhesion, ectodermal development and metabolism. The relationship between gene expression and treatment outcome was further studied using Partial Least Squares Discriminant Analysis (PLS-DA). Gene ontology analysis showed that genes responding to phototherapy and highly correlated to treatment outcome were involved in oxidation reduction, growth and mitochondria organization. In particular SPATA18, a key regulator of mitochondria quality, was found to be significantly downregulated in psoriasis, and its upregulation following phototherapy was required for optimal clinical improvement. Our data suggest that oxidation reduction is a critical event for the resolution of psoriatic plaques.
2013-12-23 | GSE53431 | GEO
Project description:Our group recently described a population of antigen presenting cells that appear to be critical in psoriasis pathogenesis, termed inflammatory myeloid dendritic cells (CD11c+ BDCA1-). Triggering receptor expressed on myeloid cells type-1 (TREM-1) signaling was a major canonical pathway in the published transcriptome of these cells. TREM-1 is a member of the immunoglobulin superfamily, active through the DAP12 signaling pathway, with an unknown ligand. Activation through TREM-1 induces inflammatory cytokines including IL-8, MCP/CCL2 and TNF. We now show that TREM-1 was expressed in the skin of healthy and psoriatic patients, and there was increased soluble TREM-1 in the circulation of psoriasis patients. In psoriasis lesions, TREM-1 was co-localized with dendritic cells as well as CD31+ endothelial cells. TREM-1 expression was reduced with successful NB-UVB, etanercept and anti-IL-17 treatments. An in vitro model of PGN-activated monocytes as inflammatory myeloid DCs was developed to study TREM-1 blockade, and treatment with a TREM-1 blocking chimera decreased allogeneic Th17 activation, as well as IL-17 production. Furthermore, TREM-1 blockade of ex vivo psoriatic dendritic cells in an alloMLR also showed a decrease in IL-17. Together, these data suggest that the TREM-1 signaling pathway offers a novel therapeutic target to prevent the effects of inflammatory myeloid DCs in psoriasis. Monocytes were isolated by plastic adherence, treated with TLR agonists overnight, washed twice and harvested in RTL-buffer. RNA was extracted and processed for microarray. 3 groups and 3 replicates with a paired structure across replicates
2012-11-17 | E-GEOD-42305 | biostudies-arrayexpress
Project description:We used microarry to charactarize differences in gene expression between lesional and non-lesional psoriasis skin. Our hypothethis was that IL-37 is downregulated in psoriasis.
2022-06-07 | GSE161683 | GEO
Project description:Background: Atopic dermatitis (AD) is a common inflammatory skin disease exhibiting a predominantly Th2/"T22" immune activation and a defective epidermal barrier. Narrow-band UVB (NB-UVB) is considered an efficient treatment for moderate to severe AD. In psoriasis, NB-UVB has been found to suppress the Th1/Th17 immune polarization with subsequent reversal of epidermal hyperplasia. The immunomodulatory effects of this treatment are largely unknown in AD. Our study evaluates the effects of NB-UVB on immune and barrier abnormalities in AD, aiming to establish reversibility of disease and biomarkers of therapeutic response. Methods: 12 moderate-to-severe chronic AD patients received NB-UVB phototherapy 3 times weekly for up to 12 weeks. Lesional and non-lesional skin biopsies were obtained before and after treatment and evaluated by gene-expression and immunohistochemistry studies. Results: All patients had at least a 50% reduction in SCORing of AD (SCORAD) index with NB-UVB phototherapy. The Th2, T22, and Th1 immune pathways were suppressed and measures of epidermal hyperplasia and differentiation also normalized after phototherapy. The reversal of disease activity was associated with elimination of inflammatory leukocytes, Th2/"T22"-associated cytokines and chemokines, and normalized expression of barrier proteins. Conclusions: Our study shows reversal of both the epidermal defects and underlying immune activation in AD. By determining the correlation of variables with therapeutic response, we have defined a set of biomarkers of disease response that associate resolved Th2 and T22 inflammation with reversal of barrier pathology. This data supports the "inside-out" hypothesis of AD, suggesting that it is a disease primarily driven by an immune stimulus. genomic profiling of treatment effect of NB-UVB in AD in both lesional and non-lesional AD skin from 10 patients. Treatment effect, disease state analysis
2011-07-01 | E-GEOD-27887 | biostudies-arrayexpress
Project description:Phototherapy is an effective therapy and may induce remission of psoriasis. Previous studies have established the action spectrum of clearance and that apoptosis is differentially induced in psoriasis plaques by clinically effective wavelengths of ultraviolet B (UVB). The aim of this study was to investigate the molecular mechanisms regulating psoriasis plaque resolution by studying the transcriptomic response to clinically effective (311nm, narrow band) UVB compared to a clinically ineffective (290nm) wavelength. We irradiated lesional psoriatic skin in vivo with a single 3 MED (minimal erythemal dose) of 311nm or 290nm wavelength of UVB and performed skin biopsies at 4h or 18h post irradiation and from un-irradiated lesional skin. Forty-eight micro-dissected epidermal samples were analysed using the Illumina DASL array platform from 20 psoriatic patients. Bioinformatic analysis identified differentially expressed genes (DEGs) associated with 311nm but not 290nm irradiation; these DEGs were subject to Ingenuity pathway and upstream regulator analysis. The number of differentially regulated epidermal genes was greatest at 18h following UVB, after irradiation with clinically effective (311nm) UVB. The main pathways differentially affected by 311nm UVB only were apoptosis, necrosis, acute phase signalling, p53 signalling and chemotaxis. The greatest fold change observed was a 7.5 fold increase in expression of CDKN1A (WAF1/ p21), the p53 target gene, following irradiation with 311nm UVB but not 290nm (clinically ineffective UVB). Acute phase, LXR and PTEN signalling, dendritic cell maturation, granulocyte adhesion and atherosclerotic pathways were also differentially regulated by 311nm compared to 290nm UVB. This work provides insight into the molecular mechanisms regulating psoriatic remodelling in response to UV phototherapy, supports a key role for apoptosis and cell death in psoriasis plaque clearance, and identifies a number of novel therapeutic pathways. Further studies may lead to development of potential biomarkers to assess which patients are more likely to respond to UVB.
2021-04-21 | GSE162998 | GEO
Project description:Purpose: To identify the gene expression and upstream regulator at lesional skin of psoriasis vulgaris Methods:Full-thickness skin biopsies at lesional skin and uninvolved skin were taken from psoriasis patients. Transcriptomic profiling was constructed by high-throughput next-generation sequencing (NGS) technology Result:The total of 1328 DEGs are identified. Among these 1328 DEGs, 648 were upregulated and 680 were down regulated . Upstream regulators involving in keratinocyte proliferation was predicted to be activated. These DEGs and upstream regulator may be associated with psoriasis pathogenesis Conclusion: This study revealed upstream regulator that may be involved in psoriasis pathogenesis
2022-10-11 | GSE186117 | GEO
Project description:Our group recently described a population of antigen presenting cells that appear to be critical in psoriasis pathogenesis, termed inflammatory myeloid dendritic cells (CD11c+ BDCA1-). Triggering receptor expressed on myeloid cells type-1 (TREM-1) signaling was a major canonical pathway in the published transcriptome of these cells. TREM-1 is a member of the immunoglobulin superfamily, active through the DAP12 signaling pathway, with an unknown ligand. Activation through TREM-1 induces inflammatory cytokines including IL-8, MCP/CCL2 and TNF. We now show that TREM-1 was expressed in the skin of healthy and psoriatic patients, and there was increased soluble TREM-1 in the circulation of psoriasis patients. In psoriasis lesions, TREM-1 was co-localized with dendritic cells as well as CD31+ endothelial cells. TREM-1 expression was reduced with successful NB-UVB, etanercept and anti-IL-17 treatments. An in vitro model of PGN-activated monocytes as inflammatory myeloid DCs was developed to study TREM-1 blockade, and treatment with a TREM-1 blocking chimera decreased allogeneic Th17 activation, as well as IL-17 production. Furthermore, TREM-1 blockade of ex vivo psoriatic dendritic cells in an alloMLR also showed a decrease in IL-17. Together, these data suggest that the TREM-1 signaling pathway offers a novel therapeutic target to prevent the effects of inflammatory myeloid DCs in psoriasis.
2012-11-17 | GSE42305 | GEO
Project description:Biopsies from uninvolved and from lesional skin of 13 patients with plaque-type psoriasis. Based on paired samples, 179 genes were more than 2-fold differentially expressed in lesional skin. Experiment Overall Design: Comparative RNA expression profiles from uninvolved and lesional skin of 13 patients with mild to severe plaque-type psoriasis.
2008-11-07 | E-GEOD-6710 | biostudies-arrayexpress