KLF13 promotes SLE Pathogenesis by modifying chromatin accessibility of key proinflammatory cytokine genes [RNA-seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1165281 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30799040.fastq.gz | Fastqsanger.gz | |||
| SRR30799041.fastq.gz | Fastqsanger.gz | |||
| SRR30799042.fastq.gz | Fastqsanger.gz | |||
| SRR30799043.fastq.gz | Fastqsanger.gz | |||
| SRR30799044.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 42 |
Similar Datasets
Project description:KLF13 promotes SLE Pathogenesis by modifying chromatin accessibility of key proinflammatory cytokine genes
| PRJNA1165278 | ENA
Project description:Although significant progress has been achieved in elucidating the genetic architecture of systemic lupus erythematosus (SLE), identifying genes underlying the pathogenesis has been challenging. The NZM2410-derived lupus susceptibility Sle3 locus is associated with T cell hyperactivity and activated myeloid cells. However, candidate genes associated with these phenotypes have not been identified. Here, we narrow the Sle3 locus to a smaller genomic segment (Sle3k) and show that mice carrying Sle3k and Sle1 loci developed lupus nephritis. We identify Klf13 as the primary candidate gene upregulated in Sle3k mice and demonstrate that Klf13 upregulation is associated with genome-wide transcription changes resulting in higher levels of proinflammatory cytokines, enhanced T cell activation, and hyperresponsiveness of myeloid cells. Correspondingly, Klf13 –/– mice display striking repression of genes involved in mediating immune activation, including key proinflammatory cytokines/chemokines. Furthermore, Klf13 –/– mice show profound dysregulation in cytokine signaling pathways in myeloid cells in response to toll receptor ligands, thus revealing a key role of KLF13 in modulating myeloid cell function. Klf13 upregulation is associated with increased production of RANTES, a key chemokine in lupus nephritis, in activated T cells and the kidneys of lupus-prone mice. In sum, our findings reveal Klf13 as a key gene in the Sle3 interval in mediating lupus pathogenesis that may have implications in the rational design of new therapies for SLE and other autoimmune/inflammatory diseases.
2024-10-15 | GSE278050 | GEO
Project description:Although significant progress has been achieved in elucidating the genetic architecture of systemic lupus erythematosus (SLE), identifying genes underlying the pathogenesis has been challenging. The NZM2410-derived lupus susceptibility Sle3 locus is associated with T cell hyperactivity and activated myeloid cells. However, candidate genes associated with these phenotypes have not been identified. Here, we narrow the Sle3 locus to a smaller genomic segment (Sle3k) and show that mice carrying Sle3k and Sle1 loci developed lupus nephritis. We identify Klf13 as the primary candidate gene upregulated in Sle3k mice and demonstrate that Klf13 upregulation is associated with genome-wide transcription changes resulting in higher levels of proinflammatory cytokines, enhanced T cell activation, and hyperresponsiveness of myeloid cells. Correspondingly, Klf13 –/– mice display striking repression of genes involved in mediating immune activation, including key proinflammatory cytokines/chemokines. Furthermore, Klf13 –/– mice show profound dysregulation in cytokine signaling pathways in myeloid cells in response to toll receptor ligands, thus revealing a key role of KLF13 in modulating myeloid cell function. Klf13 upregulation is associated with increased production of RANTES, a key chemokine in lupus nephritis, in activated T cells and the kidneys of lupus-prone mice. In sum, our findings reveal Klf13 as a key gene in the Sle3 interval in mediating lupus pathogenesis that may have implications in the rational design of new therapies for SLE and other autoimmune/inflammatory diseases.
2024-10-15 | GSE278048 | GEO
Project description:KLF13 promotes SLE Pathogenesis by modifying chromatin accessibility of key proinflammatory cytokine genes [ATAC-seq]
| PRJNA1165276 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-10-15 | GSE278051 | GEO
Project description:Nrf2 (NF-E2-related factor-2) transcription factor regulates oxidative/xenobiotic stress response and also represses inflammation. However, the mechanisms how Nrf2 alleviates inflammation are still unclear. Here, we demonstrate that Nrf2 interferes with lipopolysaccharide-induced transcriptional upregulation of proinflammatory cytokines, including IL-6 and IL-1β. ChIP-seq and ChIP-qPCR analyses revealed that Nrf2 binds to the proximity of these genes in macrophages and inhibits RNA Pol II recruitment. Further, we found that Nrf2-mediated inhibition is independent of the Nrf2 binding motif and reactive oxygen species level. Murine inflammatory models further demonstrated that Nrf2 interferes with IL6 induction and inflammatory phenotypes in vivo. Thus, contrary to the widely accepted view that Nrf2 suppresses inflammation through redox control, we demonstrate here that Nrf2 opposes transcriptional upregulation of proinflammatory cytokine genes. This study identifies Nrf2 as the upstream regulator of cytokine production and establishes a molecular basis for an Nrf2-mediated anti-inflammation approach. Gene expression in BMDMs obtained from wild-type and Keap1-CKO mice. In Keap1-CKO (Keap1 flox/flox::LysM-Cre) BMDMs, Nrf2 transcription factor is activated due to Keap1-deficiency. BMDMs were obtained by a culture of bone marrow cells in the presence of M-CSF for7 days. M1-activated BMDMs were obtained by stimulation with LPS and IFNg for 6 hours, while M2-activated BMDMs were obtained by a stimulation with IL-4 for 6 hours. Two independent BMDM cultures were performed, and each experiment contains samples obtained from one wild-type and one Keap1-CKO mice, respectively.
2016-05-12 | E-GEOD-71263 | biostudies-arrayexpress
Project description:Nrf2 (NF-E2-related factor-2) transcription factor regulates oxidative/xenobiotic stress response and also represses inflammation. However, the mechanisms how Nrf2 alleviates inflammation are still unclear. Here, we demonstrate that Nrf2 interferes with lipopolysaccharide-induced transcriptional upregulation of proinflammatory cytokines, including IL-6 and IL-1β. ChIP-seq and ChIP-qPCR analyses revealed that Nrf2 binds to the proximity of these genes in macrophages and inhibits RNA Pol II recruitment. Further, we found that Nrf2-mediated inhibition is independent of the Nrf2 binding motif and reactive oxygen species level. Murine inflammatory models further demonstrated that Nrf2 interferes with IL6 induction and inflammatory phenotypes in vivo. Thus, contrary to the widely accepted view that Nrf2 suppresses inflammation through redox control, we demonstrate here that Nrf2 opposes transcriptional upregulation of proinflammatory cytokine genes. This study identifies Nrf2 as the upstream regulator of cytokine production and establishes a molecular basis for an Nrf2-mediated anti-inflammation approach.
2016-05-12 | GSE71263 | GEO
Project description:The present gene expression array study of fluvastatin effects on monocytes from SLE patients show that fluvastatin has a global anti-inflammatory effect on monocytes, which includes attenuated expression of several proinflammatory cytokines, and regulated expression of molecules mediating lipoprotein signaling and cholesterol metabolism, as well as atherosclerosis and inflammatory signaling. Twenty seven SLE patients were given 20mg/day fluvastatin for one month. Blood samples were obtained before the starting of the treatment and at the end of treatment. Total RNA from monocytes was extracted using TRIzol reagent. RNA quality control was performed in a 2100 Bioanalyzer. Complementary RNAs from six SLE patients (four before treatment and two after treatment) were prepared for hybridization in an Agilent G4112F platform (Whole human Genome microarray 44K) using the One-color gene expression system (Agilent technologies).
2014-03-12 | E-GEOD-45422 | biostudies-arrayexpress
Project description:The inflammatory response plays out over time in a reproducible and organized manner after an initiating stimulus. Here we showed that the genes activated in cultured mouse fibroblasts in response to the proinflammatory cytokine tumor necrosis factor can be divided roughly into three groups, each with different induction kinetics. Whereas differential transcription is important in determining the grouping of these genes, differential mRNA stability also exerted strong influence in some cases overriding that of transcriptional control elements on the temporal order of gene expression. mRNA transcripts expressed early after TNF stimulation have abundant AU-rich elements in their 3'-untranslated regions whereas those expressed later are contain fewer AU-rich sequences. Thus mRNA stability and transcriptional control, two intrinsic characteristics of genes, control the kinetics of proinflammatory cytokine-induced gene expression. Experiment Overall Design: The gene expression levels were monitored in the mouse embryonic cells stimulated with TNF for 0, 0.5h, 2h and 12 hours.
2009-01-18 | E-GEOD-14071 | 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. 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