Addiction of primary cutaneous gamma-delta T-cell lymphomas to JAK-STAT signaling
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1184839 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Addiction of primary cutaneous gamma-delta T-cell lymphomas to JAK-STAT signaling
| PRJNA1184840 | ENA
Project description:Primary Cytotoxic T Cell Lymphomas Harbor Recurrent Targetable Alterations in the JAK-STAT Pathway
| PRJNA746634 | ENA
Project description:Primary Cytotoxic T Cell Lymphomas Harbor Recurrent Targetable Alterations in the JAK-STAT Pathway
| PRJNA746635 | ENA
Project description:Here we investigated the effects of JAK/STAT pharmacological inhibition on cHL cell models using ruxolitinib, a JAK 1/2 inhibitor. We use five classical Hodgkin lymphoma cell lines: L428, L1236, L540, KMH2, L591
2021-10-15 | GSE185818 | GEO
Project description:Toxic epidermal necrolysis (TEN) is a fatal cutaneous adverse drug reaction and an emerging public health issue 1-3. Triggered by common medications, patients suffer from fulminant epidermal detachment and long-term sequalae. Although molecular mechanisms driving keratinocyte cytotoxicity have been reported, no effective therapy exists4-6. In recent years, powerful omics technologies have expanded into spatial context and we reasoned that single cell spatial proteomics could uncover novel therapeutic targets in TEN. Applying Deep Visual Proteomics7,8 to formalin fixed paraffin embedded archived skin-tissue biopsies of three types of cutaneous drug reactions with varying severity quantified over 5,000 proteins in keratinocytes and skin-infiltrating immune cells. Most strikingly, this revealed a robust enrichment of Type-I- and -II interferon signature in the immune cell and keratinocyte compartment of TEN patients, along with a drastic activation of pSTAT1. Targeted inhibition with pan-JAK inhibitor (JAKi) Tofacitinib reduced keratinocyte-directed cytotoxicity in a novel live-cell imaging assay, using patient-derived keratinocytes and PBMCs. Furthermore, oral administration of pan-JAKi Tofacitinib or Baricitinib ameliorated clinical and histological disease severity in two distinct mouse models of TEN. This study uncovers the JAK-STAT and interferon signaling pathways as key pathogenic drivers of TEN and demonstrates the potential of targeted JAK inhibition as a curative therapy.
2025-01-13 | PXD044477 | Pride
Project description:Immune cells need to sustain a state of constant alertness over a lifetime. Yet, little is known about the regulatory processes that control the fluent and fragile balance that is called homeostasis. Here we demonstrate that JAK-STAT signaling, beyond its role in immune responses, is a major regulator of immune cell homeostasis. We investigated JAK-STAT-mediated transcription and chromatin accessibility across 12 mouse models, including knockouts of all STAT transcription factors and of the TYK2 kinase. Baseline JAK-STAT signaling was detected in CD8+ T cells and macrophages of unperturbed mice – but abrogated in the knockouts and in unstimulated immune cells deprived of their normal tissue context. We observed diverse transcription-regulatory programs, including gene regulation by STAT2 and IRF9 independent of STAT1. In summary, our large-scale dataset and integrative analysis of JAK-STAT mutant and wildtype mice uncovered a crucial role of JAK-STAT signaling in unstimulated immune cells, where it contributes to a poised epigenetic and transcription-regulatory state and helps prepare these cells for rapid response to immune stimuli.
2024-02-24 | GSE204734 | GEO
Project description:Immune cells need to sustain a state of constant alertness over a lifetime. Yet, little is known about the regulatory processes that control the fluent and fragile balance that is called homeostasis. Here we demonstrate that JAK-STAT signaling, beyond its role in immune responses, is a major regulator of immune cell homeostasis. We investigated JAK-STAT-mediated transcription and chromatin accessibility across 12 mouse models, including knockouts of all STAT transcription factors and of the TYK2 kinase. Baseline JAK-STAT signaling was detected in CD8+ T cells and macrophages of unperturbed mice – but abrogated in the knockouts and in unstimulated immune cells deprived of their normal tissue context. We observed diverse transcription-regulatory programs, including gene regulation by STAT2 and IRF9 independent of STAT1. In summary, our large-scale dataset and integrative analysis of JAK-STAT mutant and wildtype mice uncovered a crucial role of JAK-STAT signaling in unstimulated immune cells, where it contributes to a poised epigenetic and transcription-regulatory state and helps prepare these cells for rapid response to immune stimuli.
2024-02-24 | GSE204735 | GEO
Project description:Immune cells need to sustain a state of constant alertness over a lifetime. Yet, little is known about the regulatory processes that control the fluent and fragile balance that is called homeostasis. Here we demonstrate that JAK-STAT signaling, beyond its role in immune responses, is a major regulator of immune cell homeostasis. We investigated JAK-STAT-mediated transcription and chromatin accessibility across 12 mouse models, including knockouts of all STAT transcription factors and of the TYK2 kinase. Baseline JAK-STAT signaling was detected in CD8+ T cells and macrophages of unperturbed mice – but abrogated in the knockouts and in unstimulated immune cells deprived of their normal tissue context. We observed diverse transcription-regulatory programs, including gene regulation by STAT2 and IRF9 independent of STAT1. In summary, our large-scale dataset and integrative analysis of JAK-STAT mutant and wildtype mice uncovered a crucial role of JAK-STAT signaling in unstimulated immune cells, where it contributes to a poised epigenetic and transcription-regulatory state and helps prepare these cells for rapid response to immune stimuli.
2024-02-24 | GSE227168 | GEO
Project description:Developing targeted therapy for cutaneous T cell lymphoma (CTCL) patients still requires actionable mutated genes and deregulated pathways to be identified. There is increasing evidence that activating mutations in JAK genes and deregulated JAK/STAT signaling are important mechanisms involved in multiple B and T cell malignancies, including CTCL. Therefore, in this study we focused on studying the mutational status of JAK1, JAK2 and JAK3 genes in a series of human CTCL lesions and cell lines using next-generation sequencing (NGS). We found that 7 of 48 (14.7%) of the analyzed cases harbored mutations in the JAK1 and JAK3 genes that mainly affected the pseudokinase domain of the corresponding proteins. On the basis of these results, we used a specific JAK inhibitor (INCB018424) in a series of CTCL cell lines with deregulated JAK/STAT activity. Treatment of CTCL cells with INCB018424 resulted in dose-dependent reduction of activated STAT expression, diminished cell viability, and increased apoptosis. We also studied global changes in gene expression in cells with mutated JAK1 and JAK3 proteins treated with INCB018424 and identified multiple genes that were differentially regulated by JAK/STAT signaling, such as FGF20 (upregulated) and EGR1 (downregulated). Thus, our results show that the detection of deregulated JAK/STAT signaling in CTCL lesions via JAK mutations or other surrogate markers may serve to indicate the clinical use of JAK/STAT inhibitors. 3 replicates of cells treated with DMSO or JAKi during 30 min and 3h
2015-10-31 | E-GEOD-68562 | biostudies-arrayexpress