Ontology highlight
ABSTRACT:
PROVIDER: PRJNA693312 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13486030_1.fastq.gz | Fastqsanger.gz | |||
| SRR13486030_2.fastq.gz | Fastqsanger.gz | |||
| SRR13486031_1.fastq.gz | Fastqsanger.gz | |||
| SRR13486031_2.fastq.gz | Fastqsanger.gz | |||
| SRR13486032_1.fastq.gz | Fastqsanger.gz |
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Project description:The cellular and molecular pathways affected by IL-12p40/IL-23p40 blockade with ustekinumab in the synovium of psoriatic arthritis (PsA) patients.
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Project description:Ustekinumab provides clinical benefit to psoriasis patients, but precise cellular and molecular changes underlying its therapeutic utility are not yet fully understood. To assess differences between ustekinumab responders vs. non responders in modulating specific inflammatory pathways and provide reference data for exploring molecular effects of next-generation interleukin(IL)-17 and IL-23-antagonists in psoriasis.
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Project description:Pyoderma Gangrenosum (PG) is a rare and extremely painful neutrophilic dermatosis associated with non-healing cutaneous ulcers affecting 3-10 individuals per million people. The etiology and molecular pathogenetic events of this disease are yet unknown. To investigate how this therapeutic regime shaped the underlying inflammatory response, we performed spatial transcriptomics on lesional biopsies from patients before and after ustekinumab treatment. Our study provides high resolution temporal insights into the inflammatory environment of PG lesional skin following treatment with IL-12/IL-23 blockade in two patients with classic and peristomal PG. This work highlights that while inhibition of representative cytokines of the Th1 and Th17 pathways shows promise as a treatment for PG patients, it does not dampen all active inflammatory pathways.
2024-08-28 | GSE274489 | GEO
Project description:Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis is a life-threatening autoimmune disease that often results in kidney failure caused by crescentic glomerulonephritis (ANCA-GN). To date, treatment of most patients with ANCA-GN relies on unspecific immunosuppressive agents that harbor serious adverse effects and limited efficiency. Using spatial and single-cell transcriptome analysis we characterized inflammatory niches in the kidneys of 34 patients with ANCA-GN and idenjpgied proinflammatory cytokine producing CD4+ and CD8+ T cells as a key pathogenic tissue signature. By employing digital pharmacology we then idenjpgied ustekinumab, a monoclonal antibody targeting IL-12 and IL-23 in these T cells, as promising therapeutic avenue. Based on these findings, four patients with relapsing ANCA-GN were treated with ustekinumab in combination with low-dose cyclophosphamide. Ustekinumab was given subcutaneously (90 mg) at weeks 0, 4, 12, and 24 and clinical and renal response were evaluated at week 26. Treatment induced substantial clinical response in all ANCA-GN patients, with improvements in kidney function, and Birmingham Vasculitis Activity Score, and was well tolerated. Our findings suggest that the pathogenesis-based treatment of ANCA-GN patients with ustekinumab is efficacious and warrants further investigation in clinical trials.
2024-06-28 | GSE250138 | GEO
Project description:IL-17A plays an important role in the pathology of psoriasis and psoriatic arthritis (PsA). However, the pathogenic association between the skin and joint manifestations in PsA is not completely understood. In this study, we initially observed that IL-17A and fibroblast growth factor (FGF) 7 induced endochondral ossification in the mouse entheseal histoculture. Importantly, the responses of endochondral ossification by IL-17A stimulation were strongly inhibited by the treatment of a blocking antibody to FGF receptor 2IIIb (FGFR2IIIb), which is the receptor of FGF7, suggesting that FGF7 acts as a downstream factor of IL-17A in the endochondral ossification in the culture. Next, using the animal PsA model, the administration of anti-FGFR2IIIb antibody resulted in significant suppression of ankylosing enthesitis but not dermatitis. Collectively, our findings indicate that augmented IL-17A in PsA dermatitis induces the elevation of FGF7 levels in joint enthesis, and results in the development of ankylosing enthesitis via FGF7 signaling in PsA.
2024-06-01 | GSE234831 | GEO
Project description:Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis is a life-threatening autoimmune disease that often results in kidney failure caused by crescentic glomerulonephritis (ANCA-GN). To date, treatment of most patients with ANCA-GN relies on unspecific immunosuppressive agents that harbor serious adverse effects and limited efficiency. By performing spatial and single-cell transcriptome analysis, we characterized inflammatory niches in the kidneys of 34 patients with ANCA-GN and identified pro-inflammatory, cytokine producing CD4+ (TH1 and TH17 subsets) and CD8+ T cells (TC1 and TC17-like subsets) as a key pathogenic signature. Digital pharmacology identified ustekinumab, a monoclonal antibody targeting IL-12 and IL-23 in these T cells, as the most promising therapeutic drug to target. Based on these findings, four patients with relapsing ANCA-GN were treated with ustekinumab in combination with low-dose cyclophosphamide. Ustekinumab was given subcutaneously (90 mg) at weeks 0, 4, 12, and 24 and clinical and renal responses were evaluated at week 26. This treatment was well-tolerated and induced clinical response in all ANCA-GN patients, including an improved kidney function and Birmingham Vasculitis Activity Score. Our findings suggest that the pathogenesis-based treatment of ANCA-GN patients with ustekinumab is efficacious and warrants further investigation in clinical trials.
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Project description:Alopecia areata (AA) is a prevalent disease associated with major emotional distress, and lacks effective, safe therapeutics for patients with extensive hair loss. This is the first report of hair regrowth with specific cytokine antagonism, in three patients with extensive hair loss ranging from 40% scalp involvement to alopecia universalis. Ustekinumab, an IL-12/23p40 antagonist that is highly effective in psoriasis, showed impressive ability to induce hair regrowth, coupled with suppression of inflammatory pathways and upregulation of hair keratins. Our report suggests that extensive AA is reversible using targeted treatments, opening the door for specific cytokine antagonism for this debilitating disease. We evaluated hair regrowth in three AA patients at 20 weeks after treatment with 3 subcutaneous doses of 90mg ustekinumab given at weeks 0, 4, and 16. Skin biopsies of lesional and non-lesional scalp (when available) were taken at baseline (week 0) and at week 20. We also obtained biopsies from three healthy individuals.
2015-12-08 | E-GEOD-74761 | biostudies-arrayexpress
Project description:CD69+CD103+ tissue-resident memory T-cells (TRM) are increasingly recognised as important drivers of inflammation. To decipher their potential role in inflammatory arthritis, we applied single cell, high-dimensional profiling (CyTOF and scRNAseq) to T-cells isolated from the joint of patients with psoriatic arthritis (PsA) or rheumatoid arthritis (RA). We identified three broad groups of synovial CD8+ TRM cells: cytotoxic and Treg-like TRM cells were present in the inflamed joints of patients with both PsA and RA, while CD161+CXCR6+ type 17-like TRM cells with a pro-inflammatory cytokine profile (IL-17A+TNFa+IFNg+) and a distinct transcriptomic signature and a polyclonal, but distinct TCR repertoire, were specifically enriched in the inflamed joints of patients with PsA. Type 17-like cells were also enriched in non-TRM CD8+ T-cells in PsA compared to RA. These findings add substantively to the accumulating evidence that the immunopathology of PsA and RA is different, with a particular role for type 17 cells in PsA.
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Project description:This was a phase II, randomized, placebo-controlled, double-blinded single center study (clinicaltrials.gov: NCT01806662) to investigate safety and efficacy of ustekinumab treatment in moderate-to-severe AD patients. Patients underwent 1:1 randomization using a computer generated subject randomization table by an unblinded pharmacist. to Subjects received subcutaneous ustekinumab or placebo at weeks 0, 4, and 16 with a crossover to the other agent (either ustekinumab or placebo) at weeks 16, 20, and 32 (Figure 1A) to ensure patient retention.
2019-11-20 | GSE140684 | GEO
Project description:Polysaccharide A (PSA), a capsular carbohydrate from the commensal gut bacteria Bacteroides fragilis, has been shown to possess both potent T cell-dependent pro- and anti-inflammatory properties. PSA is able to induce abscess and adhesion formation in sepsis models, but can also inhibit asthma, inflammatory bowel disease (IBD) and experimental autoimmune encephalomyelitis (EAE) through MHCII-dependent activation of CD4+ T cells. Yet, despite decades of study, the ability of PSA to balance both these pro- and anti-inflammatory responses remains poorly understood. Here we utilized an unbiased systems immunology approach consisting of RNAseq transcriptomics, high-throughput flow cytometry and Luminex analysis to characterize the full impact of PSA-mediated stimulation of CD4+ T cells. We found that exposure to PSA resulted in the upregulation and secretion of IFNγ, TNFα, IL-6 and CXCL10, consistent with an interferon responsive gene (IRG) signature. Importantly, PSA stimulation also led to expression of immune checkpoint markers Lag3, Tim3 and especially PD1, which were also enriched and sustained in the gut associated lymphoid tissue of PSA-exposed mice. Taken together, PSA responding cells display an unusual mixture of pro-inflammatory cytokines and anti-inflammatory surface receptors, consistent with the ability to both cause and inhibit inflammatory disease.
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