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MRNAseq profiling of interferon-a stimulated WT and ISG15 KO- Human-iPSC derived macrophages

ABSTRACT: ISG15 KO cells are hyperinflammatory in phenotype. In this experiment, we further explored how they respond to interferon-a stimulation and how they differ from WT cells

ORGANISM(S): Homo sapiens

PROVIDER: GSE168798 | GEO | 2022/06/07

REPOSITORIES: GEO

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mRNAseq profiling of interferon-a stimulated WT and ISG15 KO- Human-iPSC derived macrophages

Project description:mRNAseq profiling of interferon-a stimulated WT and ISG15 KO- Human-iPSC derived macrophages

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ISG15 in regulation of interferon responses

Project description:We assessed how lack of ISG15 influences the levels of transcripts after IFNa stimulation. Expression data from ISG15 deficient patients (P1, P2, P3) and control (C1, C6, C16) hTert fibroblasts

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Expression data from WT and ISG15 KO HaCaT cells stimulated with interferon-a and treated with combination treatment of Ruxolitinib, TGFb and Doxycycline

Project description:Analysis of gene expression in WT and ISG15 KO HaCaT cells, stimulated with IFNa and treated with ruxolitinib (RUX), transforming growth factor beta (TGFb) and doxycycline (DOXY) to investigate the effects of treatments on transcriptional response in the cells.

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Expression data from hiPSC derived WT and ISG15 KO endothelial cells stimulated with interferon-a and treated with itaconic acid, dimethyl itaconate, 4-octyl itaconate and ruxolitinib

Project description:Analysis of gene expression in WT and ISG15 KO endothelial cells, stimulated with IFNa and treated with Itaconic acid (IA), Dimethyl itaconate (DI), 4-octyl itaconate (4OI) and ruxolitinib (RUX) to investigate the effects of treatments on transcriptional response in the cells.

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10x single-cell RNAseq profiling of hiPSC derived WT and ISG15 KO macrophages stimulated with interferon-a and treated with itaconic acid, 4-octyl itaconate and ruxolitinib

Project description:WT and ISG15 KO macrophages were stimulated with interferon-a and treated with itaconic acid and 4-octyl itaconate as they are known for anti-inflammatory effects. In this experiment, we further explored how itaconic acid and 4-octyl itaconate can play its role keeping ruxolitinib as a positive control in order to inhibit JAK/STAT pathway

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Network analysis identifies proinflammatory plasma cell polarization for secretion of ISG15 in human autoimmunity

Project description:Plasma cells (PCs) as effectors of humoral immunity produce immunoglobulins to match pathogenic insult. However, emerging data suggests more diverse roles for PCs as regulators of immune and inflammatory responses via secretion of factors other than immunoglobulins. The extent to which such responses are pre-programmed in B-lineage cells or can be induced in PCs by the microenvironment is unknown. Here we dissect the impact of IFNs on the regulatory networks of human plasma cells. We show that core PC programs are unaffected, while PCs respond to IFNs with distinctive transcriptional responses. The ISG15-system emerges as a major transcriptional output induced in a sustained fashion by IFN-Î± in PCs and linked both to intracellular conjugation and ISG15 secretion. This leads to the identification of ISG15-secreting plasmablasts/PCs in patients with active SLE. Thus ISG15-secreting PCs represent a distinct pro-inflammatory PC subset providing an immunoglobulin-independent mechanism of PC action in human autoimmunity B-cells were isolated from the peripheral blood of three adult donors and differentiated in vitro (see individual samples for culture conditions)

2016-07-22 | E-GEOD-75007 | biostudies-arrayexpress

Network analysis identifies proinflammatory plasma cell polarization for secretion of ISG15 in human autoimmunity

Project description:Plasma cells (PCs) as effectors of humoral immunity produce immunoglobulins to match pathogenic insult. However, emerging data suggests more diverse roles for PCs as regulators of immune and inflammatory responses via secretion of factors other than immunoglobulins. The extent to which such responses are pre-programmed in B-lineage cells or can be induced in PCs by the microenvironment is unknown. Here we dissect the impact of IFNs on the regulatory networks of human plasma cells. We show that core PC programs are unaffected, while PCs respond to IFNs with distinctive transcriptional responses. The ISG15-system emerges as a major transcriptional output induced in a sustained fashion by IFN-α in PCs and linked both to intracellular conjugation and ISG15 secretion. This leads to the identification of ISG15-secreting plasmablasts/PCs in patients with active SLE. Thus ISG15-secreting PCs represent a distinct pro-inflammatory PC subset providing an immunoglobulin-independent mechanism of PC action in human autoimmunity

2016-07-22 | GSE75007 | GEO

ISG15 counteracts Listeria monocytogenes infection

Project description:ISG15 counteracts Listeria monocytogenes infection

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Interferon-stimulated gene 15 (ISG15) conjugates proteins in dermatomyositis muscle with perifascicular atrophy.

Project description:We investigated interferon-stimulated gene 15 (ISG15), a poorly understood ubiquitin-like modifier, and its enzymatic pathway in dermatomyositis (DM), an autoimmune disease primarily involving muscle and skin.We generated microarray data measuring transcript abundance for approximately 18,000 genes in each of 113 human muscle biopsy specimens, and studied biopsy specimens and cultured skeletal muscle using immunohistochemistry, immunoblotting proteomics, real-time quantitative polymerase chain reaction, and laser-capture microdissection.Transcripts encoding ISG15-conjugation pathway proteins were markedly upregulated in DM with perifascicular atrophy (DM-PFA) muscle (ISG15 339-fold, HERC5 62-fold, and USP18 68-fold) compared with 99 non-DM samples. Combined analysis with publicly available microarray datasets showed that >50-fold ISG15 transcript elevation had 100% sensitivity and specificity for 28 biopsies from adult DM-PFA and juvenile DM patients compared with 199 muscle samples from other muscle diseases. Free ISG15 and ISG15-conjugated proteins were only found on immunoblots from DM-PFA muscle. Cultured human skeletal muscle exposed to type 1 interferons produced similar transcripts and ISG15 protein and conjugates. Laser-capture microdissection followed by proteomic analysis showed deficiency of titin in DM perifascicular atrophic myofibers.A large-scale microarray study of muscle samples demonstrated that among a diverse group of muscle diseases DM was uniquely associated with upregulation of the ISG15 conjugation pathway. Exposure of human skeletal muscle cell culture to type 1 interferons produced a molecular picture highly similar to that seen in human DM muscle. Perifascicular atrophic myofibers in DM were deficient in a number of skeletal muscle proteins including titin.

| S-EPMC2875060 | biostudies-literature

The prognostic significance of interferon-stimulated gene 15 (ISG15) in invasive breast cancer.

Project description:BackgroundLymphovascular invasion (LVI) is a prognostic factor in early-stage invasive breast cancer (BC). Through bioinformatics, data analyses of multiple BC cohorts revealed the positive association between interferon-stimulated gene 15 (ISG15) LVI status. Thus, we explored the prognostic significance of ISG15 in BC.MethodsThe prognostic significance of ISG15 mRNA was assessed in METABRIC (n = 1980), TCGA (n = 854) and Kaplan-Meier Plotter (n = 3951). ISG15 protein was evaluated using immunohistochemistry (n = 859) in early-stage invasive BC patients with long-term follow-up. The associations between ISG15 expression and clinicopathological features, expression of immune cell markers and patient outcome data were evaluated.ResultsHigh mRNA and protein ISG15 expression were associated with LVI, higher histological grade, larger tumour size, hormonal receptor negativity, HER2 positivity, p53 and Ki67. High ISG15 protein expression was associated with HER2-enriched BC subtypes and immune markers (CD8, FOXP3 and CD68). High ISG15 mRNA and ISG15 expressions were associated with poor patient outcome. Cox proportional multivariate analysis revealed that the elevated ISG15 expression was an independent prognostic factor of shorter BC-specific survival.ConclusionThis study provides evidence for the role of ISG15 in LVI development and BC prognosis. Further functional studies in BC are warranted to evaluate the therapeutic potential of ISG15.

| S-EPMC7867506 | biostudies-literature

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