Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1204203 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR31850650_1.fastq.gz | Fastqsanger.gz | |||
| SRR31850650_2.fastq.gz | Fastqsanger.gz | |||
| SRR31850651_1.fastq.gz | Fastqsanger.gz | |||
| SRR31850651_2.fastq.gz | Fastqsanger.gz | |||
| SRR31850652_1.fastq.gz | Fastqsanger.gz |
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Project description:Innate immune PRRs sense nucleic acids from microbes and orchestrate cytokine production to resolve infection. Inappropriate recognition of host nucleic acids also results in autoimmune disease. Here we utilize a model of inflammation resulting from accrual of self DNA (DNase II-/- Ifnar-/-) to understand the role of PRR sensing pathways in arthritis and autoantibody production. Using mice deficient in DNase II/Ifnar together with deficiency in either STING or AIM2 (TKO), we reveal central roles for the STING and AIM2 pathway in arthritis. AIM2 TKO mice show limited inflammasome activation and, like STING TKO mice, have reduced inflammation in joints. Surprisingly, autoantibody production is maintained in AIM2 and STING TKO mice, while DNase II-/- Ifnar-/- mice also deficient in Unc93b, a chaperone required for TLR7/9 endosomal localization, fail to produce autoantibodies to nucleic acids. Collectively, these data support distinct roles for cytosolic and endosomal nucleic acid sensing pathways in disease manifestations.
2014-12-25 | GSE63503 | GEO
Project description:We report positional cloning and characterization of a novel Sting allele that fails to activate IFN production in the wild-derived mice of MOLF/Ei strain in response to HSV (Herpes Simplex Virus) and Listeria monocytogenes both in vitro and in vivo. We show that previously uncharacterized mutations in the N-terminal of STING are responsible for low levels of IFN due to failure of MOLF STING to respond to cytosolic STING agonists such as 2â3âcGAMP, 5,6-Dimethylxanthenone-4-acetic acid (DMXAA) or poly(deoxyadenylic-deoxythymidylic) acid (dAdT). Using Next-Generation Sequencing (NGS) for the analysis of DNA-responses in congenic C57BL6.StingMOLF/MOLF (MOLF STING) mouse macrophages, we show that these mutations in MOLF/Ei discriminate in responses between different STING agonists. Macrophages from C57BL6.StingB6/B6¬ (B6 STING), or B6 STING expressing littermates were stimulated as a positive control for STING activation, and STING -/- (STING KO) macrophages served as a negative control. To examine differential gene regulation downstream of murine Tmem173 (STING) allelic variants. We stimulated macrophages from B6 mice congenic for MOLF STING; macrophages from B6 STING expressing littermates were stimulated as a positive control for STING activation, and STING -/- (STING KO) macrophages served as a negative control. One replicate of RNA-seq reads after each stimulation provided. Conditions are peritoneal macrophages from B6 congenic mice expressing: B6 STING, MOLF STING, or STING KO stimulated with 2â3âcGAMP, 5,6-Dimethylxanthenone-4-acetic acid (DMXAA), poly(deoxyadenylic-deoxythymidylic) acid (dAdT), or no treatment. This constitutes a total of 12 reads analyzed in this data set.
2016-07-05 | E-GEOD-68140 | biostudies-arrayexpress
Project description:The transcription factor Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is activated by the metabolite itaconate during metabolic reprogramming. Activated Nrf2 then dampens the release of pro-inflammatory cytokines and type I IFNs in response to toll-like receptor stimulation. If and how Nrf2 affects cytosolic antiviral sensing and whether this occurs during metabolic reprogramming is currently not known. Here, we show that Nrf2 is a negative regulator of the adaptor molecule STimulator of INterferon Genes (STING), which signals downstream of the cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS). The regulation of STING by Nrf2 was inducible by the metabolite itaconate, specific to human cells, and sufficient to decrease the responsiveness to STING agonists and to increase the susceptibility to infection with DNA viruses. Mechanistically, Nrf2 regulated STING expression post-transcriptionally by increasing STING mRNA stability. Lastly, treatment with itaconate or with the chemical Nrf2 inducer sulforaphane repressed STING expression and the release of type I IFNs in cells from patients with the STING dependent interferonopathy SAVI. With this report we identify Nrf2 as an important regulator of cGAS-STING signaling pathway and link metabolic reprogramming to control of cytosolic DNA sensing.
2018-05-01 | GSE113519 | GEO
Project description:STING molecule has been reported to be important adaptor molecule for cytosolic DNA sensing. We investigated gene expression by cytosolic DNA stimulation using bone marrow derived dendritic cells. We comparared gene expression profile between WT and STING knock out BMDCs after cytosolic DNA stimulation. We generated BMDCs by culturing in the presence of GM-CSF. BMDCs were stimulated by purified tumor-cell derived DNA using lipofectamine. After 7 hrs incubation, total RNA was isolated using Rneasy kit (Qiagen) and microarray was performed at genomic core facility in university of Chicago
2014-09-30 | E-GEOD-61835 | biostudies-arrayexpress
Project description:We report positional cloning and characterization of a novel Sting allele that fails to activate IFN production in the wild-derived mice of MOLF/Ei strain in response to HSV (Herpes Simplex Virus) and Listeria monocytogenes both in vitro and in vivo. We show that previously uncharacterized mutations in the N-terminal of STING are responsible for low levels of IFN due to failure of MOLF STING to respond to cytosolic STING agonists such as 2’3’cGAMP, 5,6-Dimethylxanthenone-4-acetic acid (DMXAA) or poly(deoxyadenylic-deoxythymidylic) acid (dAdT). Using Next-Generation Sequencing (NGS) for the analysis of DNA-responses in congenic C57BL6.StingMOLF/MOLF (MOLF STING) mouse macrophages, we show that these mutations in MOLF/Ei discriminate in responses between different STING agonists. Macrophages from C57BL6.StingB6/B6¬ (B6 STING), or B6 STING expressing littermates were stimulated as a positive control for STING activation, and STING -/- (STING KO) macrophages served as a negative control.
2016-01-03 | GSE68140 | GEO
Project description:STING molecule has been reported to be important adaptor molecule for cytosolic DNA sensing. We investigated gene expression by cytosolic DNA stimulation using bone marrow derived dendritic cells. We comparared gene expression profile between WT and STING knock out BMDCs after cytosolic DNA stimulation.
2014-09-30 | GSE61835 | GEO
Project description:Interferons (IFN) are induced by sensing of self and non-self RNA or DNA by pathogen recognition receptors. In particular, the aberrant accumulation of cytosolic nucleic acids or the accumulation of DNA lesions has the potential to activate the STING pathway to induce IFNs. While aberrant self-DNA sensing can cause autoimmunity, negative regulators keep these under check. Here we report that MEF2A is a novel negative regulator of inflammation which suppresses the induction of IFNs at homeostasis. We show that MEF2A deficiency results in the spontaneous induction of type I IFN and robust downstream ISG expression in a STING-dependent and cGAS-independent manner. We demonstrate that the IFN response elicited by MEF2A depletion could protect cells from cardiotropic virus infections. We found that the loss of MEF2A triggered the replicative stress response to promote a DDX41/STING-dependent induction type I IFN response. The replicative stress response is dependent on ATR kinase activity, as inhibition of ATR abrogated STING activation and type I IFN production. Thus, our study connects MEF2A with protection from maladaptive type I IFN responses due to replicative stress response across various cell types as well as links the DDX41-dependent activation of STING to the replicative stress response.
2023-10-01 | GSE209601 | GEO
Project description:Stimulator of interferon genes (STING) is a central component of the cytosolic nucleic acids sensing pathway and as such master regulator of the type I interferon response. Due to its critical role in physiology and its’ involvement in a variety of diseases, STING has been a focus for drug discovery. Targeted protein degradation (TPD) has emerged as a promising pharmacology for targeting previously considered undruggable proteins by hijacking the cellular ubiquitin proteasome system (UPS) with small molecules. Here, we identify AK59 as a STING degrader leveraging HERC4, a HECT-domain E3 ligase. Additionally, our data reveals that AK59 is effective on the common pathological STING mutations, suggesting a potential clinical application of this mechanism. Thus, these findings introduce HERC4 to the field of TPD and a compound-induced degradation of STING, suggesting potential therapeutic applications.
2024-04-12 | PXD046677 | Pride
Project description:The complement system mediates diverse regulatory effects across the immune system. C5aR2, an enigmatic receptor for anaphylatoxin C5a, has been shown to modulate PRR-dependent pro-inflammatory cytokine secretion in human macrophages. However, the specific downstream targets and underlying molecular mechanisms are less defined. In this study, CRISPR-Cas9 was used to generate macrophage models lacking C5aR2, which were used to probe the role of C5aR2 in the context of PRR stimulation. cGAS and STING-induced IFN-β secretion was significantly increased in C5aR2 KO THP-1 cells and C5aR2-edited primary human monocyte-derived macrophages, and expression of STING and IRF3 was increased in C5aR2 KO cell lines, implicating C5aR2 as a regulator of the IFN-β response to cGAS-STING pathway activation. Transcriptomic analysis by RNAseq revealed that nucleic acid sensing and antiviral signalling pathways were significantly up-regulated in C5aR2 KO THP-1 cell lines. These results suggest that C5aR2 is a negative regulator of nucleic acid sensing in macrophages, with potential relevance for viral infection and anti-tumour immunity.
2023-10-22 | GSE245973 | GEO
Project description:ATR inhibition potentiates ionizing radiation-induced interferon response via cytosolic nucleic acid-sensing pathways
| PRJNA630762 | ENA