Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Astrocytic RIPK3 exerts protective anti-inflammatory activity during viral encephalitis via induction of serpin protease inhibitors

ABSTRACT: Astrocytic RIPK3 exerts protective anti-inflammatory activity during viral encephalitis via induction of serpin protease inhibitors

PROVIDER: PRJNA1117499 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other
	SRR29207900_1.fastq.gz	Fastqsanger.gz
	SRR29207900_2.fastq.gz	Fastqsanger.gz
	SRR29207894_1.fastq.gz	Fastqsanger.gz
	SRR29207894_2.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 7

Similar Datasets

Astrocytic RIPK3 exerts protective anti-inflammatory activity during viral encephalitis via induction of serpin protease inhibitors

Project description:Flaviviruses pose a significant threat to public health due to their ability to infect the central nervous system (CNS) and cause severe neurologic disease. Astrocytes play a crucial role in the pathogenesis of flavivirus encephalitis through their maintenance of blood-brain barrier (BBB) integrity and their modulation of immune cell recruitment and activation within the CNS. We have previously shown that receptor interacting protein kinase-3 (RIPK3) is a central coordinator of neuroinflammation during CNS viral infection, a function that occurs independently of its canonical function in inducing necroptotic cell death. To date, however, roles for necroptosis-independent RIPK3 signaling in astrocytes are poorly understood. Here, we use mouse genetic tools to induce astrocyte-specific deletion, overexpression, and chemogenetic activation of RIPK3 to demonstrate an unexpected anti-inflammatory function for astrocytic RIPK3. RIPK3 activation in astrocytes was required for host survival in multiple models of flavivirus encephalitis, where it restricted neuropathogenesis by limiting immune cell recruitment to the CNS. Transcriptomic analysis revealed that, despite inducing a traditional pro-inflammatory transcriptional program, astrocytic RIPK3 paradoxically promoted neuroprotection through the upregulation of serpins, endogenous protease inhibitors with broad immunomodulatory activity. Notably, intracerebroventricular administration of SerpinA3N in infected mice preserved BBB integrity, reduced leukocyte infiltration, and improved survival outcomes in mice lacking astrocytic RIPK3. These findings highlight a previously unappreciated role for astrocytic RIPK3 in suppressing pathologic neuroinflammation and suggests new therapeutic targets for the treatment of flavivirus encephalitis.

2025-06-01 | GSE268520 | GEO

Neuronal DAMPs exacerbate neurodegeneration via astrocytic RIPK3 signaling

Project description:Astrocyte activation is a common feature of neurodegenerative diseases. However, the ways in which dying neurons influence the activity of astrocytes is poorly understood. RIPK3 signaling has recently been described as a key regulator of neuroinflammation, but whether this kinase mediates astrocytic responsiveness to neuronal death has not yet been studied. Here, we used the MPTP model of Parkinson’s disease to show that activation of astrocytic RIPK3 drives dopaminergic cell death and axon damage. Transcriptomic profiling revealed that astrocytic RIPK3 promoted gene expression associated with neuroinflammation and movement disorders, and this coincided with significant engagement of DAMP signaling. Using human cell culture systems, we show that factors released from dying neurons signal through RAGE to induce RIPK3-dependent astrocyte activation. These findings highlight a mechanism of neuron-glia crosstalk in which neuronal death perpetuates further neurodegeneration by engaging inflammatory astrocyte activation via RIPK3.

2024-04-05 | GSE237891 | GEO

Neuronal DAMPs exacerbate neurodegeneration via astrocytic RIPK3 signaling

Project description:Neuronal DAMPs exacerbate neurodegeneration via astrocytic RIPK3 signaling

| PRJNA996993 | ENA

Encephalitis and poor neuronal death-mediated control of herpes simplex virus in human inherited RIPK3 deficiency

Project description:We hypothesize that human RIPK3 deficiency does not result in impairment of type I IFN mediated antiviral immunity, contrasting with the situation in deficiencies of the TLR3-IFNAR1 circuit. To test the cellular responses to HSV1 at the wide transcriptome level, bulk RNA sequencing was performed with human primary fibroblasts without or with HSV-1 infection for 24 hours, in cells from healthy controls, RIPK3 HSE patient and other patients with recessive TLR3, IFNAR1 or NEMO deficiency.

2023-03-29 | GSE228495 | GEO

Idenitifying RIPK3 dependent genes in neurons expressing RIPK3-activatable system

Project description:The transcriptional potential of RIPK3 in a non-infectious system in neurons is unclear. Here we found that RIPK3 activation, independent of any upstream signals is sufficient to induce anti-viral transcription in neurons.

2025-05-07 | GSE280962 | GEO

Ubiquitylation of RIPK3 beyond-the-RHIM limits RIPK3 activity and cell death

Project description:Pathogen recognition receptors and TNF superfamily members engage Receptor Interacting Serine/threonine Kinase-3 (RIPK3) to activate programmed cell death, including MLKL-mediated necroptosis and caspase-8-dependent apoptosis. However, the post-translational control of RIPK3 signalling is not fully understood. Using mass-spectrometry, we identified a novel ubiquitylation site on murine RIPK3 beyond the RIP homotypic interaction motif (RHIM) on K469. Complementation of RIPK3-deficient cells with a Ripk3K469R mutant demonstrated that the decoration of RIPK3 K469 by ubiquitin limits both RIPK3-mediated caspase-8 activation and apoptotic killing, in addition to RIPK3 autophosphorylation and MLKL-mediated necroptosis. Unexpectedly, the overall ubiquitylation of mutant RIPK3K469R was enhanced, which largely resulted from additional RIPK3 ubiquitylation on K359. Loss of RIPK3 K359 ubiquitylation reduced RIPK3K469R hyper-ubiquitylation and limited the ability of Ripk3K469R/K469R to trigger enhanced killing. Ripk3K469R/K469R mice challenged with Salmonella displayed increased bacterial loads in the spleen and liver, with reduced IFN serum levels. Therefore, RIPK3 K469 ubiquitylation can function to prevent RIPK3 ubiquitylation on alternate lysine residues, which otherwise promote RIPK3 oligomerization and consequent cell death signalling.

2022-08-12 | PXD026533 | Pride

Transcriptional profiles of PA1 teratoma cells transfected by RIPK1, RIPK2, RIPK3, or RIPK4

Project description:RIPK4 but not the related kinases RIPK1, RIPK2, and RIPK3 caused similar transcriptional changes to Wnt3a. PA1 cells were transfected by 8ug RIPK1, RIPK2, RIPK3, or RIPK4 for 48h, RNA were extracted and sequenced.

2013-02-04 | E-GEOD-43362 | biostudies-arrayexpress

Assessing RIPK3 dependent genes in death-resistant and death-susceptible MEFs encoding activatable RIPK3-system

Project description:The full transcriptional RIPK3-dependent transcriptional potential in MEFs is unknown. Here, we found that RIPK3 is a dominant driver of anti-viral and inflammatory transcription in MEFs.

2025-05-07 | GSE281061 | GEO

IM015 - Influenza infection of C57BL6 and RIPK3 knock-out mice

Project description:This purpose of this experiment was to investigate the transcriptional differences between C57BL6, RIPK3 knock-out mice infected with influenza strain A/CA/04/2009 (H1N1) virus. Overview of Experiment: Groups of 6-8 week-old C57BL6 and RIPK3 knock-out mice were infected with influenza A/CA/04/2009 virus. Infections were done at 10^5 PFU or time-matched mock infected. Time points were 2 and 4 d.p.i. There were 2-3 animals/dose/time point. Lung samples were collected for virus load and transcriptional analysis. Weight loss and animal survival were also monitored.

2014-04-02 | E-GEOD-51526 | biostudies-arrayexpress

Idenitifying RIPK3 dependent genes in neurons expressing RIPK3-activatable system

Project description:Idenitifying RIPK3 dependent genes in neurons expressing RIPK3-activatable system

| PRJNA1181549 | ENA