IRF3 and type I interferons fuel a fatal response to myocardial infarction
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ABSTRACT:
PROVIDER: PRJNA416978 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6257520.fastq.gz | Fastqsanger.gz | |||
| SRR6256351_1.fastq.gz | Fastqsanger.gz | |||
| SRR6256351_2.fastq.gz | Fastqsanger.gz | |||
| SRR6257521_1.fastq.gz | Fastqsanger.gz | |||
| SRR6257521_2.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Interferon regulatory factor 3 (IRF3) and type I interferons (IFNs) protect against infections1 and cancer2, but excessive IRF3 activation and type I IFN production cause autoinflammatory conditions such as Aicardi?Goutières syndrome3,4 and STING-associated vasculopathy of infancy (SAVI)3. Myocardial infarction (MI) elicits inflammation5, but the dominant molecular drivers of MI-associated inflammation remain unclear. Here we show that ischemic cell death and uptake of cell debris by macrophages in the heart fuel a fatal response to MI by activating IRF3 and type I IFN production. In mice, single-cell RNA-seq analysis of 4,215 leukocytes isolated from infarcted and non-infarcted hearts showed that MI provokes activation of an IRF3?interferon axis in a distinct population of interferon-inducible cells (IFNICs) that were classified as cardiac macrophages. Mice genetically deficient in cyclic GMP-AMP synthase (cGAS), its adaptor STING, IRF3, or the type I IFN receptor IFNAR exhibited impaired interferon-stimulated gene (ISG) expression and, in the case of mice deficient in IRF3 or IFNAR, improved survival after MI as compared to controls. Interruption of IRF3-dependent signaling resulted in decreased cardiac expression of inflammatory cytokines and chemokines and decreased inflammatory cell infiltration of the heart, as well as in attenuated ventricular dilation and improved cardiac function. Similarly, treatment of mice with an IFNAR-neutralizing antibody after MI ablated the interferon response and improved left ventricular dysfunction and survival. These results identify IRF3 and the type I IFN response as a potential therapeutic target for post-MI cardioprotection.
2017-11-06 | GSE106471 | GEO
Project description:Interferon regulatory factor 3 (IRF3) and type I interferons (IFNs) protect against infections1 and cancer2, but excessive IRF3 activation and type I IFN production cause autoinflammatory conditions such as Aicardi?Goutières syndrome3,4 and STING-associated vasculopathy of infancy (SAVI)3. Myocardial infarction (MI) elicits inflammation5, but the dominant molecular drivers of MI-associated inflammation remain unclear. Here we show that ischemic cell death and uptake of cell debris by macrophages in the heart fuel a fatal response to MI by activating IRF3 and type I IFN production. In mice, single-cell RNA-seq analysis of 4,215 leukocytes isolated from infarcted and non-infarcted hearts showed that MI provokes activation of an IRF3?interferon axis in a distinct population of interferon-inducible cells (IFNICs) that were classified as cardiac macrophages. Mice genetically deficient in cyclic GMP-AMP synthase (cGAS), its adaptor STING, IRF3, or the type I IFN receptor IFNAR exhibited impaired interferon-stimulated gene (ISG) expression and, in the case of mice deficient in IRF3 or IFNAR, improved survival after MI as compared to controls. Interruption of IRF3-dependent signaling resulted in decreased cardiac expression of inflammatory cytokines and chemokines and decreased inflammatory cell infiltration of the heart, as well as in attenuated ventricular dilation and improved cardiac function. Similarly, treatment of mice with an IFNAR-neutralizing antibody after MI ablated the interferon response and improved left ventricular dysfunction and survival. These results identify IRF3 and the type I IFN response as a potential therapeutic target for post-MI cardioprotection.
2017-11-06 | GSE106472 | GEO
Project description:IRF3 and type I interferons fuel a fatal response to myocardial infarction [bulk RNA-Seq]
| PRJNA417168 | ENA
Project description:IRF3 and type I interferons fuel a fatal response to myocardial infarction [single cell RNA-Seq]
| PRJNA417199 | ENA
Project description:Interferon regulatory factor 3 (IRF3) and type I interferons (IFNs) protect against infections and cancer, but excessive IRF3 activation and type I IFN production cause autoinflammatory conditions such as Aicardi-Goutières syndrome and STING-associated vasculopathy of infancy (SAVI). Myocardial infarction (MI) elicits inflammation, but the dominant molecular drivers of MI-associated inflammation remain unclear. Here we show that ischemic cell death and uptake of cell debris by macrophages in the heart fuel a fatal response to MI by activating IRF3 and type I IFN production. In mice, single-cell RNA-seq analysis of 4,215 leukocytes isolated from infarcted and non-infarcted hearts showed that MI provokes activation of an IRF3-interferon axis in a distinct population of interferon-inducible cells (IFNICs) that were classified as cardiac macrophages. Mice genetically deficient in cyclic GMP-AMP synthase (cGAS), its adaptor STING, IRF3, or the type I IFN receptor IFNAR exhibited impaired interferon-stimulated gene (ISG) expression and, in the case of mice deficient in IRF3 or IFNAR, improved survival after MI as compared to controls. Interruption of IRF3-dependent signaling resulted in decreased cardiac expression of inflammatory cytokines and chemokines and decreased inflammatory cell infiltration of the heart, as well as in attenuated ventricular dilation and improved cardiac function. Similarly, treatment of mice with an IFNAR-neutralizing antibody after MI ablated the interferon response and improved left ventricular dysfunction and survival. These results identify IRF3 and the type I IFN response as a potential therapeutic target for post-MI cardioprotection.
| S-EPMC6477926 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2017-11-06 | GSE106473 | GEO
Project description:The interferon regulatory factors IRF3 and IRF7 are key players in the regulation of type I and III IFN genes. In this study, we analyzed the role of IRF3 and IRF7 for the host response to influenza A virus infections in Irf3-/-, Irf7-/- and Irf3-/-Irf7-/- knock-out mice.
2016-11-02 | GSE77600 | GEO
Project description:IRF3 is one of the most critical transcription factor in down stream of pattern recognition receptors (such as toll-like receptor and RIG-I-like receptor) signalling pathway. IRF3 is known to induce the expression of type I IFN gene upon virus infection. To furter examine the role of IRF3 in virus-induced gene expression, we preformed microarray analysis in IRF3-/- peritoneal macrophages infected with VSV, and found that IRF3 suppresses the expression of Il12b gene. Peritoneal macrophages from WT of IRF3-/- B6 mice were infected with VSV(1 M.O.I. ) for 6 hous, and then subjected to microarray analysis.
2012-05-19 | E-GEOD-37855 | biostudies-arrayexpress