Homo sapiens
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ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-38351
PROVIDER: PRJNA168483 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The multifaceted balance of TNF-a and type I / II interferon responses in SLE and RA: how monocytes manage the impact of cytokines
2025-01-24 | E-GEOD-38351 | ExpressionAtlas
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: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.
2012-06-14 | GSE38351 | GEO
Project description:Whole blood expression was profiled in Rheumatoid Arthiritis and SLE (Systemic LUPUS Erythomatosus) patients. Expression in the whole blood of RA and SLE patients, comparing gene expression signatures in SLE, and RA DMARD-IR and RA TNF-IR patients. This is baseline whole blood expression data for 3 patient populations (SLE, RA DMARD-IR and RA TNF-IR) and 20 Controls.
2015-05-14 | E-GEOD-45291 | biostudies-arrayexpress
Project description:Objective: Gene expression studies performed on PBMC from systemic lupus erythematosus (SLE) patients provided strong evidence of a type I interferon signature, underscoring the potential role of these cytokines in the physiopathology of SLE. In this work, we performed microarray analyses of differential gene expression using purified CD4 T and B cells sorted from SLE PBMC. In order to discriminate genes specific to SLE from those induced by inflammatory responses in general, control samples were obtained not only from healthy individuals but also from rheumatoid arthritis (RA) patients. Results: A strong interferon signature was found both in the CD4 T and the B lymphocytes from SLE patients, thereby confirming the results obtained on total PBMC. Interestingly, many interferon-induced genes were also over-expressed in CD4 and B cells from RA patients. Some genes were more specifically over-expressed in SLE lymphocytes, and 3 of them, SLAMF1, BRDG1 and RASGRP1, were exclusively up-regulated in SLE B cells. SLAMF1 and BRDG1 are localized in disease-associated loci, thereby suggesting that they might play a role in the physiopathology of the disease. Experiment Overall Design: CD4 T and B cells were sorted by flow cytometry from PBMC of patients with SLE, RA and healthy controls. GeneChip® Human genome U133 Plus 2.0 arrays were hybridized in monoplicates and the genes differentially expressed among the three groups of patients were identified using ANOVA tests with corrections for multiple comparisons.
2008-06-13 | E-GEOD-4588 | biostudies-arrayexpress
Project description:SLE patients are always with various disease manifestation. Various cytokines are pointed interacting and playing pathological roles in SLE although the etiopathology is still obscure. In this study, we aimed to investigate the effects of cytokine interactions in the immune response of SLE patients. Overexpressed interferon-inducible(IFI) genes were confirmed in peripheral blood from SLE patients. Using network-based analysis on the immune response-related genes, several networks including cytokines such as TNF and IFN-γ, or beta-estradiol(E2), were constructed. TNF-regulated genes were dominant in these networks but in vitro TNF stimulation on PBMCs showed no different responses in the expressions of these genes between SLE and healthy individuals. Co-stimulating experiments by TNF, IFN-γ, and E2 with IFN-α, revealed that TNF has repressive while IFN-γ essentially has synergistic effect with IFN-α on IFI gene expressions in vitro. E2 showed different effects on IFI gene expressions among 3 individuals. Peripheral blood was obtained from patients with SLE (n=11) and healthy women (n=6). Gene expression profile was analyzed using DNA microarray covering 30,000 human genes. Differentially expressed immune response-related genes were selected and analyzed by using Expression Analysis Systemic Explorer (EASE) based on Gene Ontology (GO) followed by network pathway analysis with Ingenuity Pathways Analysis (IPA).
2009-05-31 | E-GEOD-12374 | biostudies-arrayexpress
Project description:SLE patients are always with various disease manifestation. Various cytokines are pointed interacting and playing pathological roles in SLE although the etiopathology is still obscure. In this study, we aimed to investigate the effects of cytokine interactions in the immune response of SLE patients. Overexpressed interferon-inducible(IFI) genes were confirmed in peripheral blood from SLE patients. Using network-based analysis on the immune response-related genes, several networks including cytokines such as TNF and IFN-γ, or beta-estradiol(E2), were constructed. TNF-regulated genes were dominant in these networks but in vitro TNF stimulation on PBMCs showed no different responses in the expressions of these genes between SLE and healthy individuals. Co-stimulating experiments by TNF, IFN-γ, and E2 with IFN-α, revealed that TNF has repressive while IFN-γ essentially has synergistic effect with IFN-α on IFI gene expressions in vitro. E2 showed different effects on IFI gene expressions among 3 individuals.
2009-06-01 | GSE12374 | GEO
Project description:Objective: Gene expression studies performed on PBMC from systemic lupus erythematosus (SLE) patients provided strong evidence of a type I interferon signature, underscoring the potential role of these cytokines in the physiopathology of SLE. In this work, we performed microarray analyses of differential gene expression using purified CD4 T and B cells sorted from SLE PBMC. In order to discriminate genes specific to SLE from those induced by inflammatory responses in general, control samples were obtained not only from healthy individuals but also from rheumatoid arthritis (RA) patients. Results: A strong interferon signature was found both in the CD4 T and the B lymphocytes from SLE patients, thereby confirming the results obtained on total PBMC. Interestingly, many interferon-induced genes were also over-expressed in CD4 and B cells from RA patients. Some genes were more specifically over-expressed in SLE lymphocytes, and 3 of them, SLAMF1, BRDG1 and RASGRP1, were exclusively up-regulated in SLE B cells. SLAMF1 and BRDG1 are localized in disease-associated loci, thereby suggesting that they might play a role in the physiopathology of the disease. Keywords: Comparative analysis of global gene expression in PBMC subsets
2006-12-31 | GSE4588 | GEO
Project description:<p><strong>BACKGROUND:</strong> SLE is a complex autoimmune disease with deleterious effects on various organs. Accumulating evidence has shown abnormal vitamin B12 and one-carbon flux contribute to immune dysfunction. Transcobalamin II (TCN2) belongs to the vitamin B12-binding protein family responsible for the cellular uptake of vitamin B12. The role of TCN2 in SLE is still unclear.</p><p><strong>METHODS:</strong> We collected clinical information and blood from 51 patients with SLE and 28 healthy controls. RNA sequencing analysis, qPCR and western blot confirmed the alteration of TCN2 in disease monocytes. The correlation between TCN2 expression and clinical features and serological abnormalities was analyzed. TCN2 heterozygous knockout THP1 cells were used to explore the effects of TCN2 dysfunction on monocytes. CCK-8 assay and EdU staining were used to detect cell proliferation. ELISA was conducted to assess vitamin B12, glutathione and cytokines changes. UHPLC-MRM-MS/MS was used to detect changes in the intermediates of the one-carbon cycle. Flow cytometry is used to detect cell cycle, ROS, mitoROS and CD14 changes.</p><p><strong>RESULTS:</strong> Elevated TCN2 in monocytes was correlated positively with disease progression and specific tissue injuries. Using CD14+ monocytes and TCN2 genetically modified THP1 cell lines, we found that the TCN2 was induced by LPS in serum from SLE patients. TCN2 heterozygous knockout inhibited cellular vitamin B12 uptake and one-carbon metabolism, leading to cell proliferation arrest and decreased Toll-like receptor 4 (TLR4)-mediated CCL2 release. Methionine cycle metabolites, s-adenosylmethionine and homocysteine, rescued these effects, whereas folate treatment proved to be ineffective. Folate deficiency also failed to replicate the impact of TCN2 downregulation on THP1 inflammatory response.</p><p><strong>CONCLUSION:</strong> Our study elucidated the unique involvement of TCN2-driven one-carbon flux on SLE-associated monocyte behavior. Increased TCN2 may promote disease progression and tissue damage by enhancing one-carbon flux, fostering monocyte proliferation and exacerbating TLR4 mediated inflammatory responses. The inhibition of TCN2 may be a promising therapeutic approach to ameliorate SLE.</p>
1970-01-01 | MTBLS9136 | MetaboLights
Project description:The effect of human immunodeficiency virus (HIV) infection and high-level HIV replication on the function of monocytes was investigated. HIV-positive patients had elevated levels of spontaneous production of some or all of the monocyte proinflammatory cytokines measured (interleukin-1beta [IL-1beta], IL-6, and tumor necrosis factor alpha [TNF-alpha]) compared to uninfected controls. In patients on therapy with high frequencies of monocytes producing proinflammatory cytokines, this frequency was diminished in the context of viremia during an interruption of therapy. Diminished production of proinflammatory cytokines during viremia was restored by culture with autologous CD4(+) T cells or monocytes from an on-therapy time point or lipopolysaccharide (LPS). Microarray analysis demonstrated that diminished monocyte production of proinflammatory cytokines was correlated with elevated type I interferon-stimulated gene transcripts. The addition of exogenous alpha 2A interferon diminished the spontaneous production of IL-1beta, IL-6, and TNF-alpha but did not affect responses to LPS, recapitulating the changes observed for HIV-viremic patients. These results suggest that monocyte function is diminished during high-level HIV viremia and that this effect is mediated by chronic stimulation by type I interferons. This effect on monocytes during viremia may play a role in diminished innate or adaptive immune system functions in HIV-infected patients. In addition, the restoration of these functions may also play a role in some immune reconstitution syndromes observed during initiation of therapy.
2007-10-26 | E-GEOD-5220 | biostudies-arrayexpress