SLE serum induced transcripts regulated by IFNa2b
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE46921 | GEO | 2014/06/03
SECONDARY ACCESSION(S): PRJNA203035
REPOSITORIES: GEO
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Project description:To explore the full extent of IFN-regulated transcriptional changes, we exposed monocytes from two healthy donors to recombinant type I IFN (IFN-α2b) in vitro. RNA was extracted at different incubation times (1, 6, 24, 48 and 72 hrs) and the expression data was normalized to that of monocytes cultured with medium.
2014-06-03 | GSE46911 | GEO
Project description:To explore the full extent of IFN-regulated transcriptional changes, we exposed monocytes from two healthy donors to recombinant type I IFN (IFN-M-NM-12b) in vitro. RNA was extracted at 6 hrs and the expression data was normalized to that of monocytes cultured with medium. Blood monocytes isolated from healthy volunteers were incubated with 20% autologous serum alone or in the presence of 1000 U/ml of IFNM-NM-12b (Schering Plough, Kenilworth, NJ) in 6-well plates at a concentration of 106 monocytes per well in 3 ml of media. After incubation for six hours at 37 M-bM-^AM-0C, cells were harvested and RNA was extracted.
2014-06-03 | E-GEOD-46921 | biostudies-arrayexpress
Project description:To explore the full extent of IFN-regulated transcriptional changes, we exposed monocytes from two healthy donors to recombinant type I IFN (IFN-M-NM-12b) in vitro. RNA was extracted at different incubation times (1, 6, 24, 48 and 72 hrs) and the expression data was normalized to that of monocytes cultured with medium. Blood monocytes isolated from healthy volunteers were incubated with 20% autologous serum alone or in the presence of 1000 U/ml of IFNM-NM-12b (Schering Plough, Kenilworth, NJ) in 6-well plates at a concentration of 106 monocytes per well in 3 ml of media. After incubation for one hour at 37 M-bM-^AM-0C, cells were harvested and RNA was extracted. Identical experiments were done after the following incubation time points: six hours, twenty four hours, two days, and three days.
2014-06-03 | E-GEOD-46911 | biostudies-arrayexpress
Project description:Monocytes from 3 healthy donors were cultured for 6 hours in the presence of 20% serum from three newly diagnosed, untreated SLE patients. Microarray analysis was then performed upon normalizing the gene expression levels of samples incubated with SLE sera to those incubated with autologous serum. Monocytes from 3 healthy donors were cultured for 6 hours in the presence of 20% serum from three newly diagnosed, untreated SLE patients. Microarray analysis was then performed upon normalizing the gene expression levels of samples incubated with SLE sera to those incubated with autologous serum.
2014-06-03 | E-GEOD-46920 | biostudies-arrayexpress
Project description:Monocytes from 3 healthy donors were cultured for 6 hours in the presence of 20% serum from three newly diagnosed, untreated SLE patients. Microarray analysis was then performed upon normalizing the gene expression levels of samples incubated with SLE sera to those incubated with autologous serum.
2014-06-03 | GSE46920 | GEO
Project description:To better characterize the molecules that could potentially confer antigen presenting capacity to SLE monocytes, we assessed their gene expression profile. Blood monocytes from five healthy controls and five pediatric SLE patients were isolated using CD14+ selection. Because drugs used to treat SLE could induce considerable transcriptional changes, we selected active, newly diagnosed patients who had never received oral or intravenous (IV) medications.
2014-06-03 | E-GEOD-46907 | biostudies-arrayexpress
Project description:To better characterize the molecules that could potentially confer antigen presenting capacity to SLE monocytes, we assessed their gene expression profile.
2014-06-03 | GSE46907 | GEO
Project description:Many cytokines are involved in the pathogenesis of autoimmune diseases and are recognized as relevant therapeutic targets to attenuate inflammation, such as TNFα in RA and IFNα/γ in SLE. To relate the transcriptional imprinting of cytokines in a cell type-specific and disease-specific manner, we generated gene-expression profiles from peripheral monocytes of SLE and RA patients and compared them to in vitro-generated signatures induced by TNFα, IFNα2a and IFNγ. Monocytes from SLE and RA patients revealed disease-specific gene-expression profiles. In vitro-generated signatures induced by IFNα2a and IFNγ showed similar profiles that only partially overlapped with those induced by TNFα. Comparisons between disease-specific and in vitro-generated signatures identified cytokine-regulated genes in SLE and RA with qualitative and quantitative differences. The IFN-responses in SLE and RA were found to be regulated in a STAT1-dependent and STAT1-independent manner, respectively. Similarly, genes recognized as TNFα-regulated were clearly distinguishable between RA and SLE patients. While the activity of SLE monocytes was mainly driven by IFN, the activity from RA monocytes showed a dominance of TNFα that was characterized by STAT1 down-regulation. The responses to specific cytokines were revealed to be disease-dependent and reflected the interplay of cytokines within various inflammatory milieus. This study has demonstrated that monocytes from RA and SLE patients exhibit disease-specific gene-expression profiles, which can be molecularly dissected when compared to in vitro-generated cytokine signatures. The results suggest that an assessment of cytokine-response status in monocytes may be helpful for improvement of diagnosis and selection of the best cytokine target for therapeutic intervention. Expression profiles of human peripheral blood monocytes activated in vivo and stimulated in vitro. Monocytes from patients with SLE and RA and from healthy donors were used for generating disease-specific gene-expression profiles, where these profiles represent in vivo activation of monocytes. In addition, monocytes from healthy donors were stimulated in vitro by cytokines: TNFα, IFNα2a and IFNγ. Cytokine-specific gene-expression profiles were generated by comparing stimulated monocytes with unstimulated ones. TNFα-, IFNα2a- and IFNγ as cytokine-specific gene-expression profiles were compared with RA and SLE, as disease-specific gene-expression profiles.
2012-06-13 | E-GEOD-38351 | biostudies-arrayexpress
Project description:Monocytes/macrophages are activated in several autoimmune diseases, including systemic sclerosis (scleroderma, SSc), with increased expression of IFN-regulatory genes and inflammatory cytokines, suggesting dysregulation of the innate immune response in autoimmunity. Recently, we found that EBV is deregulated in SSc with abnormal expression of viral lytic-genes in PBMCs and skin. Since monocytes/macrophages are involved in innate immune recognition of EBV/lytic infection, we sought to determine whether EBV might contribute to their activation in SSc. In this study, using recombinant-EBV we infected monocytes from SSc and healthy donors (HDs), we found that viral replication is essential for inducing the expression of TLR8 in EBV-infected primary monocytes. Markers of activated monocytes, such as IFN-regulated genes and chemokines, were up-regulated in SSc- and HD-EBV-infected monocytes. Inhibiting TLR8 expression reduced virally-induced-TLR8 in THP-1 infected cells, demonstrating that innate immune activation by infectious EBV is partially dependent on TLR8. Viral lytic-mRNA and -proteins were detected in freshly isolated SSc monocytes. Microarray analysis substantiated the evidence of an increased IFN signature and altered level of TLR8 expression in SSc monocytes carrying infectious EBV compared to HD monocytes.
2017-06-12 | GSE86984 | GEO
Project description:Objective: Patients with Systemic Lupus Erythematosus (SLE) have an ongoing interferon (IFN) production due to an activation of plasmacytoid dendritic cells (pDCs), which can be triggered to type I IFN synthesis by RNA containing immune complexes (RNA-IC). Considering emerging data suggesting a role of type III interferon (IFN) in the SLE disease process, we asked if RNA-IC can induce type III IFN production in pDC, and how this production can be regulated. Methods: Peripheral blood mononuclear cells (PBMCs) or immune cell subsets were isolated from healthy blood donors or SLE patients and stimulated with IC containing U1 snRNP and SLE-IgG (RNA-IC). Hydroxychloroquine (HCQ) and an interleukin receptor 1 associated kinase 4 inhibitor (IRAK4i) were added to cell cultures. Cytokine mRNA levels were determined with a microarray and protein levels with immunoassays. Single-cell RNA-sequencing of pDCs using ddSEQ technology was performed. Results: Type III IFN mRNA and protein was induced in RNA-IC stimulated pDC-NK and pDC-B cell co-cultures. A subset of activated pDCs (3%) expressed both type III and type I IFN mRNA. IFN-λ2, IFN-α2b, interleukin (IL)-3, IL-6 or granulocyte-macrophage colony stimulating factor (GM-CSF) enhanced IFN-λ1/3 production 2-5-fold. HCQ and an IRAK4i blocked the RNA-IC-triggered IFN-λ1/3 production (p<0.01). IFN-α2b and GM-CSF increased the proportion of SLE patients producing IFN-λ1/3 in response to RNA-IC from 11 to 33%. Conclusions: Type III IFN production is triggered by RNA-IC in pDCs in a TLR-MyD88-dependent manner, enhanced by NK and B cells as well as several pro-inflammatory cytokines. These results support a contributing role for both type I and type III IFNs in SLE, which needs to be considered when targeting the IFN system in this disease.
2020-05-23 | GSE149415 | GEO