Immunoprofiling of Darier Disease patients
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE222043 | GEO | 2023/09/23
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, qPCR and immunohistochemistry, we demonstrate enhanced expression of Th-17-related genes and cytokines in six 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 to significant clinical improvement. As DD is a chronic, relapsing disease, our findings provide new options for the long-term management of skin inflammation in patients with DD.
2023-09-25 | GSE235255 | GEO
Project description:Immunoprofiling of prostate cancer infiltrate
| PRJNA644438 | ENA
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:SLE patients exhibit increased interferon signatures in their skin secondary to increased production and a robust, skewed IFN response that is regulated by PITX1. Targeting of these exaggerated pathways may prove to be beneficial to prevent and treat hyperinflammatory responses in SLE skin.
2019-01-15 | GSE124939 | GEO
Project description:We found that T cells and tumor cells are differentially dependent on Atp2a2 for their survival. In fact, Atp2a2 KO T cells have increased function, whereas Atp2a2 KO tumor cells die. Thapsigargin is a drug that targets the protein product of Atp2a2: Serca2b. We found that in tumor cells, the SAGA complex transmits TG signals to induce tumor cell death, principally via Ccdc101.
2023-11-10 | GSE161209 | GEO
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
Project description:We performed immunoprofiling of HTLV-1 Tax301-309 (SFHSLHLLF) specific CD8+ T cells in PB of HAM patients associated with T cell activation by single cell RNA sequencing (scRNA-seq).
2022-08-12 | GSE210786 | GEO
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:Developmental delay/intellectual disability (DD/ID)affects 2% of our population. However, most patients are often left without aspecific diagnosis,with the corresponding consequences for the patients and their families. The application of microarray technology in the study of patients with DD/ID allows whole-genome analysis with a high resolutionand performance. Here we present the results of four cases included in a series of 246 patients with DD/ID, as part of the screening of the genetic causes responsible for their phenotype.
2014-10-17 | GSE62439 | GEO
Project description:Treatment for the debilitating, chronic skin disease hidradenitis suppurativa (HS) is grossly inadequate. A better understanding of its pathogenesis is required to design new therapeutic strategies. Despite an incidence of approximately 1 in 200, HS is underrecognized and underdiagnosed, with a high morbidity and poor quality of life, which may last decades. In this study we first employed single cell RNA sequencing to analyse gene expression in immune cells isolated from HS lesions compared with healthy control skin. We identified 30 unique immune cell clusters, with a significant enrichment in the frequency of plasma cells, Th17 cells and a subset of dendritic cells (DC) in HS skin. These findings were validated by flow cytometry, which revealed a significant increase in infiltrating immune cells in HS skin, including T cells, B cells, neutrophils, dermal macrophages and DC. The sequencing analysis revealed that the immune transcriptome in HS skin was distinct and much more heterogenous, when compared with healthy skin. Genes and pathways associated with Th17 cells and IL-17, IL-1β, and the NLRP3 inflammasome were enhanced in HS skin, particularly in samples with a high inflammatory load. Inflammasome constituent genes principally mapped to Langerhans cells and a subpopulation of DC. A skin explant model showed that culture of HS skin with an NLRP3 inflammasome inhibitor reduced the inflammatory response, with significant reduction of IL-1β and IL-17A as well as other key mediators of inflammation. These data provide a rationale for targeting the IL-17 pathway in HS, particularly upstream at the NLRP3 inflammasome.
2023-10-01 | GSE212721 | GEO