Targeting of Th17-related cytokines in patients with Darier Disease
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE235255 | GEO | 2023/09/25
REPOSITORIES: GEO
Similar Datasets
Project description:Darier disease (DD) is a rare, inherited multi-organ disorder associated with mutations in the ATP2A2 gene. In DD patients, the skin is frequently affected, characterized by malodorous, inflamed skin and recurrent, severe infections. Therapeutic options are limited and inadequate for the long-term management of this chronic disease. Using immunoprofiling with NanoString technology we demonstrate enhanced expression of Th-17-related genes and cytokines in five DD patients. We prove that targeting the IL-23/-17 axis in DD with monoclonal antibodies is an effective and safe therapy in DD patients, leading also to significant clinical improvement.
2023-09-23 | GSE222043 | GEO
Project description:Immunoprofiling of Darier Disease patients
| PRJNA917428 | ENA
Project description:Background: Dupuytren’s disease (DD) is a fibro-proliferative disorder of unknown aetiology. Previous studies have implicated multiple WNT signalling genes/proteins in Dupuytren pathology, including WNT4. However, it is not yet clear whether WNT signalling dysregulation plays an important role in the initiation of the disease or progression. The aim of this study was to determine if loss of WNT4 expression triggered ‘Dupuytren-like’ changes in the transcriptome of healthy skin fibroblasts. Methods: Fibroblasts were isolated from the wrists of healthy adult males and from the wrists and disease cord tissue from males in a family positive for Dupuytren’s disease. Normal skin fibroblasts from healthy controls were treated with WNT4 siRNA and scrambled controls. RNASeq was used to analyse the transcriptomes of disease and non-disease fibroblasts from patients with Dupuytren’s as well as in siRNA treated and non-treated control fibroblasts. Results: Analysis of the transcriptomes from DD patient and normal skin fibroblasts showed significant differences, including in WNT4 expression. Downregulation of WNT4 in normal skin fibroblasts using siRNA led to ‘DD-like’ changes in the transcriptome. Conclusion: In people susceptible to DD WNT4 is downregulated even in non-fibrotic fibroblasts. Knockdown of WNT4 in normal fibroblasts led to changes that made cells ‘DD-like’. This study shows that WNT4 is down regulated in ‘non-disease’ cells, and that downregulating WNT4 in normal skin fibroblasts leads to widespread ‘DD like’ changes in the transcriptome, suggesting WNT4 downregulation is a key driver of DD.
2024-07-01 | GSE269317 | GEO
Project description:EGFR/MEK inhibitor therapy induces a distinct inflammatory hair follicle response that includes a collapse of hair follicle immune privilege and differential modulation of IL-33 and IL-37 expression. Our findings suggest that successful future management of EGFRi/MEKi-induced folliculitis requires restoration of hair follicle immune privilege. In this RNAseq parietal scalp (rather than truncal skin) biopsies were taken from long-term (3-9 months) EGFRi-treated patients exhibiting folliculitis (Chronic-EGFRi) or from patients prior to commencing and after two weeks of EGFRi therapy (Acute-EGFRi), compared to normal scalp skin.
2024-07-19 | E-MTAB-13455 | biostudies-arrayexpress
Project description:Dupuytren's disease (DD) is a classic example of pathological fibrosis which results in a debilitating disorder affecting a large sector of the human population. It is characterized by excessive local proliferation of fibroblasts and over-production of collagen and other components of the extracellular matrix (ECM) in the palmar fascia. The fibrosis progressively results in contracture of elements between the palmar fascia and skin causing flexion deformity or clawing of the fingers and a severe reduction in hand function. While much is known about the pathogenesis and surgical treatment of DD, little is known about the factors that cause its onset and progression, despite many years of research. Gene expression patterns in DD patients now offers the potential to identify genes that direct the pathogenesis of DD. In this study, we used primary cultures of fibroblasts derived from excisional biopsies of fibrotic tissue from DD patients to compare the gene expression profiles on a genome-wide basis with normal control fibroblasts. Our investigations have identified genes that may be involved with DD pathogenesis including some which are directly relevant to fibrosis. In particular, these include significantly reduced expression levels of three matrix metallopeptidases (MMP1, MMP3, MMP16), follistatin, and STAT1, and significantly increased expression levels of fibroblast growth factors (FGF9, FGF11), a number of collagen genes and other ECM genes in DD patient samples. Many of these gene products are known to be involved in fibrosis, tumour formation and in the normal processes of tissue remodelling. In addition, alternative splicing was identified in some DD-associated genes. These highly sensitive genomic investigations provide new insight into the molecular mechanisms that may underpin the development and progression of DD. Four exon arrays of DD primary fibroblasts derived from fibrotic tissue were compared to fibroblasts derived from skin punch biopsies from individuals who did not show DD symptoms.
2013-10-01 | E-GEOD-41524 | biostudies-arrayexpress
Project description:Diffuse malignant peritoneal mesothelioma (DMPM) is a rapidly lethal malignancy. The comprehension of the molecular features of DMPM is of utmost importance for the fruitful management of the disease, especially in patients who fail standard treatments and have a poor prognosis due to the lack of effective alternative therapeutic options.
2019-02-07 | GSE112154 | GEO
Project description:Hidradenitis suppurativa (HS) is a highly prevalent, morbid inflammatory skin disease with limited treatment options. The major cell types and inflammatory pathways in skin of HS patients are poorly understood. We profiled via scRNASeq myeloid cells and keratinocytes sort-purified from two healthy skin samples and two samples with HS pathology to determine major cell types and transcriptional pathways altered in HS.
2020-08-27 | GSE155850 | GEO
Project description:Cutaneous T cell lymphoma (CTCL) is defined by infiltration of activated and malignant T cells in skin. The clinical manifestations and prognosis in CTCL are highly variable. In this study, we hypothesized that gene expression analysis in lesional skin biopsies can improve understanding of the disease and its management. Based on 63 skin samples, we performed consensus clustering, revealing three patient clusters. Two clusters tended to differentiate limited CTCL (stages IA and IB) from more extensive CTCL (stages IB and III). Stage IB subjects appeared in both clusters, but those in the limited CTCL cluster were more responsive to treatment than those in the more extensive CTCL cluster. The third cluster was enriched in lymphocyte activation genes and was associated with a high proportion of tumor (stage IIB) lesions. Survival analysis revealed significant differences in event-free survival between clusters, with poorest survival seen in the activated lymphocyte cluster. Using supervised analysis, we further characterized genes significantly associated with lower stage/treatment responsive versus higher stage/treatment resistant CTCL. We conclude that transcriptional profiling of CTCL skin lesions reveals clinically relevant signatures, correlating with differences in survival and response to treatment. Additional prospective long-term studies to validate and refine these findings appear warranted. Experiment Overall Design: 63 skin biopsies from patients with different stages of disease were selected for RNA extraction and hybridization on Affymetrix microarrays
2008-06-16 | E-GEOD-9479 | biostudies-arrayexpress
Project description:Here, we report the first complete genomes of three cultivable treponeme species from bovine digital dermatitis (DD) skin lesions, two comparative human treponemes and a bovine gastrointestinal (GI) isolate. Key genomic differences between bovine and human treponemes implicate microbial mechanisms that enhance knowledge of how DD, a severe disease of ruminants, has emerged into a prolific and endemic disease in countries worldwide. Bovine DD treponemes have additional oxidative stress genes compared to nearest human-isolated relatives, suggesting better toleration of oxidative stress, and thus potentially explaining the ability of bovine strains to colonize skin surfaces. Comparison of bovine DD and GI treponemes as well as bovine pathogenic and human non-pathogenic saprophyte Treponema phagedenis strains indicates genes encoding a five-enzyme biosynthetic pathway for the production of 2,3-diacetamido-2,3-dideoxy-d-mannuronic acid, a rare di-N-acetylated mannuronic acid sugar with potential immunomodulatory activity, as important for pathogenesis. The bovine T. phagedenis strains further differed from human strains by having a larger number of unique genetic features including components of a type IV secretion system and a phosphate utilisation system including phoU, a gene associated with enhanced osmotic stress survival. Proteomic analyses confirmed bovine derived T. phagedenis exhibits expression of PhoU but not the putative secretion system whilst the novel mannuronic acid pathway was expressed in near entirety across the DD treponemes. Analysis of osmotic stress response in water identified a difference between bovine and human T. phagedenis with bovine strains surviving better. This novel mechanism could enable a selective advantage, allowing environmental persistence and transmission of bovine T. phagedenis. Finally, we investigated a range of treponeme genes encoding ortholog families across the DD treponemes representing putative outer membrane proteins (OMPs) and identified several families as multi-specific adhesins capable of binding extra cellular matrix (ECM) components. Human saprophytic T. phagedenis could not be differentiated from bovine pathogenic strains by these adhesins and only two of ten characterised ortholog OMP families were absent from commensal bovine treponemes. One of these bovine pathogen specific adhesin ortholog families showed considerable diagnostic potential with the Treponema medium representative demonstrating the greatest disease specificity (91.6%). This work has shed light on treponeme host adaptation and has identified candidate molecules for future diagnostics, vaccination and therapeutic intervention.
2021-03-16 | PXD022419 | Pride
Project description:Dupuytren's disease (DD) is a classic example of pathological fibrosis which results in a debilitating disorder affecting a large sector of the human population. It is characterized by excessive local proliferation of fibroblasts and over-production of collagen and other components of the extracellular matrix (ECM) in the palmar fascia. The fibrosis progressively results in contracture of elements between the palmar fascia and skin causing flexion deformity or clawing of the fingers and a severe reduction in hand function. While much is known about the pathogenesis and surgical treatment of DD, little is known about the factors that cause its onset and progression, despite many years of research. Gene expression patterns in DD patients now offers the potential to identify genes that direct the pathogenesis of DD. In this study, we used primary cultures of fibroblasts derived from excisional biopsies of fibrotic tissue from DD patients to compare the gene expression profiles on a genome-wide basis with normal control fibroblasts. Our investigations have identified genes that may be involved with DD pathogenesis including some which are directly relevant to fibrosis. In particular, these include significantly reduced expression levels of three matrix metallopeptidases (MMP1, MMP3, MMP16), follistatin, and STAT1, and significantly increased expression levels of fibroblast growth factors (FGF9, FGF11), a number of collagen genes and other ECM genes in DD patient samples. Many of these gene products are known to be involved in fibrosis, tumour formation and in the normal processes of tissue remodelling. In addition, alternative splicing was identified in some DD-associated genes. These highly sensitive genomic investigations provide new insight into the molecular mechanisms that may underpin the development and progression of DD.
2013-10-01 | GSE41524 | GEO