Narrow-band UVB phototherapy reverses DNA methylation changes in psoriatic epidermis
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Xiaolian Gu
PROVIDER: E-GEOD-63315 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:To obtain a comprehensive DNA methylation signature specific for the epidermal component of psoriasis and to analyze methylation changes during therapy, we performed genome-wide DNA methylation profiling of epidermal cells from 12 patients undergoing narrow-band UVB phototherapy and 12 corresponding healthy controls. A distinct DNA methylation pattern was seen in psoriasis compared to controls. An overall hypomethylation was found in psoriasis and 3665 methylation variable positions were identified. The DNA methylation pattern was reversed at the end of phototherapy in patients with clinical response.
2015-04-02 | GSE63315 | 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.
2013-12-23 | GSE53431 | 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: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.
2011-07-01 | GSE27887 | 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:We have discovered that human vitiligo patients treated with narrow-band UVB (NBUVB) demonstrated localized resistance to repigmentation in skin sites characterized by distinct cellular and molecular pathways. We used the remaining slides from our immunostaining studies. 1.0 mm2 epidermal scrapes were collected from formalin fixed paraffin embedded (FFPE) transverse sections of biopsies from four paired responding and non-responding vitiligo lesions (8 samples total), following published work (Trejo et al., 2019; Yeakley). The material collected was subjected to whole transcriptome TempO-Seq assay. We used a novel method that combines epidermal scraping and TempO-Seq transcriptome analysis and found that the abnormal environment in non-responding was driven by dysregulated cAMP and WNT/β-catenin signaling pathways. Characterization of abnormal environment that prevents vitiligo repigmentation may open roads for discovery of new drugs that reverse depigmentation.
2024-02-27 | GSE256271 | GEO
Project description:BackgroundThe sun is a natural source of UV radiation. It can be divided into three bands, UVA (315-400 nm), UVB (280-315 nm) and UVC (100-280 nm), where the radiation up to 290 nm is very effectively eliminated by the stratospheric ozone. Although UV radiation can have a beneficial effect on our organism and can be used in the treatment of several skin diseases, it must primarily be considered harmful.MethodsIn the presented work, we focused on the study of the longer-wavelength UV components (UVA and UVB) on the human epidermal keratinocyte line HaCaT. As UVA and UVB radiation sources, we used commercially available UVA and UVB tubes from Philips (Philips, Amsterdam, The Netherlands), which are commonly employed in photochemotherapy. We compared their effects on cell viability and proliferation, changes in ROS production, mitochondrial function and the degree of DNA damage.ResultsOur results revealed that UVB irradiation, even with significantly lower irradiance, caused greater ROS production, depolarization of mitochondrial membrane potential and greater DNA fragmentation, along with significantly lowering cell viability and proliferative capacity.ConclusionsThese results confirm that UV radiation causes severe damages in skin cells, and they need to be protected from it, or it needs to be applied more cautiously, especially if the component used is UVB.
| S-EPMC8656598 | biostudies-literature
Project description:Whether epidermal factors play a primary role in immune-mediated skin diseases such as psoriasis is unknown. We now show that the pro-differentiation transcription factor Grainyhead-like 3 (GRHL3), essential during epidermal development but dispensable in adult skin homeostasis, is required for barrier repair after adult epidermal injury. Consistent with activation of a GRHL3-regulated repair pathway in psoriasis, we find GRHL3 up-regulation in lesional skin where GRHL3 binds known epidermal differentiation gene targets. Furthermore, we show the functionality of this pathway in the Imiquimod mouse model of immune-mediated epidermal hyperplasia where loss of Grhl3 exacerbates the epidermal damage response, conferring greater sensitivity to disease induction, delayed resolution of epidermal lesions, and resistance to anti-IL-22 therapy. ChIP-seq and gene expression profiling studies show that while GRHL3 regulates differentiation genes both in development and during repair from immune-mediated damage, it targets distinct sets of genes in the two processes. In particular, GRHL3 suppresses a number of alarmin and other pro-inflammatory genes after immune injury. This study identifies a GRHL3-regulated epidermal barrier repair pathway that suppresses disease initiation and helps resolve existing lesions in immune-mediated epidermal hyperplasia. A single timepoint was assessed after physical injury of the epidermal barrier and two timepoints were assessed after immune mediated injury of the epidermis following Imiquimod treatment (psoriasis mouse model)
2014-10-01 | E-GEOD-59384 | biostudies-arrayexpress
Project description:The recent worldwide rise in idiopathic immune and inflammatory diseases such as multiple sclerosis (MS) and inflammatory bowel diseases (IBD) has been linked to Western society-based changes in lifestyle and environment. These include decreased exposure to sunlight/UVB light and subsequent impairment in the production of vitamin D, as well as dysbiotic changes in the makeup of the gut microbiome. Despite their association, it is unclear if there are any direct links between UVB light and the gut microbiome. In this study we investigated whether exposing the skin to Narrow Band Ultraviolet B (NB-UVB) light to increase serum vitamin D levels would also modulate the makeup of the human intestinal microbiota. The effects of NB-UVB light were studied in a clinical pilot study using a healthy human female cohort (n = 21). Participants were divided into those that took vitamin D supplements throughout the winter prior to the start of the study (VDS+) and those who did not (VDS-). After three NB-UVB light exposures within the same week, the serum 25(OH)D levels of participants increased on average 7.3 nmol/L. The serum response was negatively correlated to the starting 25-hydroxy vitamin D [25(OH)D] serum concentration. Fecal microbiota composition analysis using 16S rRNA sequencing showed that exposure to NB-UVB significantly increased alpha and beta diversity in the VDS- group whereas there were no changes in the VDS+ group. Bacteria from several families were enriched in the VDS- group after the UVB exposures according to a Linear Discriminant Analysis (LDA) prediction, including Lachnospiracheae, Rikenellaceae, Desulfobacteraceae, Clostridiales vadinBB60 group, Clostridia Family XIII, Coriobacteriaceae, Marinifilaceae, and Ruminococcus. The serum 25(OH)D concentrations showed a correlation with the relative abundance of the Lachnospiraceae, specifically members of the Lachnopsira and Fusicatenibacter genera. This is the first study to show that humans with low 25(OH)D serum levels display overt changes in their intestinal microbiome in response to NB-UVB skin exposure and increases in 25(OH)D levels, suggesting the existence of a novel skin-gut axis that could be used to promote intestinal homeostasis and health. Clinical Trial Registration: clinicaltrials.gov, NCT03962673. Registered 23 May 2019 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03962673?term=NCT03962673&rank=1.
| S-EPMC6821880 | biostudies-literature
Project description:BackgroundAtopic dermatitis (AD) is a common inflammatory skin disease exhibiting a predominantly T(H)2/"T22" immune activation and a defective epidermal barrier. Narrow-band UVB (NB-UVB) is considered an efficient treatment for moderate-to-severe AD. In patients with psoriasis, NB-UVB has been found to suppress T(H)1/T(H)17 polarization, with subsequent reversal of epidermal hyperplasia. The immunomodulatory effects of this treatment are largely unknown in patients with AD.ObjectiveWe sought to evaluate the effects of NB-UVB on immune and barrier abnormalities in patients with AD, aiming to establish reversibility of disease and biomarkers of therapeutic response.MethodsTwelve patients with moderate-to-severe chronic AD received NB-UVB phototherapy 3 times weekly for up to 12 weeks. Lesional and nonlesional skin biopsy specimens were obtained before and after treatment and evaluated by using gene expression and immunohistochemistry studies.ResultsAll patients had at least a 50% reduction in SCORAD index scores with NB-UVB phototherapy. The T(H)2, T22, and T(H)1 immune pathways were suppressed, and measures of epidermal hyperplasia and differentiation normalized. The reversal of disease activity was associated with elimination of inflammatory leukocytes and T(H)2/T22- associated cytokines and chemokines and normalized expression of barrier proteins.ConclusionsOur study shows that resolution of clinical disease in patients with chronic AD is accompanied by reversal of both the epidermal defects and the underlying immune activation. We have defined a set of biomarkers of disease response that associate resolved T(H)2 and T22 inflammation in patients with chronic AD with reversal of barrier pathology. By showing reversal of the AD epidermal phenotype with a broad immune-targeted therapy, our data argue against a fixed genetic phenotype.
| S-EPMC3448950 | biostudies-literature