Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cellular spermine targets JAK1 to restrain cytokine-mediated autoimmunity (Mouse)

ABSTRACT: Combining metabolomics analyses with an IFN-stimulated response elements reporter system, we identify spermine as a cellular metabolite brake for JAK1 signaling. Spermine directly binds to FERM and SH2 domains of JAK1 to impair IFNAR2-JAK1 interaction. Spermine suppresses JAK1 phosphorylation triggered by types I and II cytokines, including IFN-I/II, IL-2, and IL-6. Spermine treatment attenuates autoimmune pathogenesis in a SLE murine model and reduces IFN-I signaling in monocytes from SLE patients, which have reduced spermine levels.

ORGANISM(S): Mus musculus

PROVIDER: GSE222887 | GEO | 2024/06/21

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Cellular spermine targets JAK1 to restrain cytokine-mediated autoimmunity

Project description:Combining metabolomics analyses with an IFN-stimulated response elements reporter system, we identify spermine as a cellular metabolite brake for JAK1 signaling. Spermine directly binds to FERM and SH2 domains of JAK1 to impair IFNAR2-JAK1 interaction. Spermine suppresses JAK1 phosphorylation triggered by types I and II cytokines, including IFN-I/II, IL-2, and IL-6. Spermine treatment attenuates autoimmune pathogenesis in a SLE murine model and reduces IFN-I signaling in monocytes from SLE patients, which have reduced spermine levels.

2024-06-21 | GSE218731 | GEO

Cellular spermine controls autoinflammation by targeting JAK1 to restrain cytokine response

Project description:Using an unbiased metabolomics approach and a IFN-stimulated response elements (ISRE) reporter screening system, we have identified the cellular metabolite spermine as an endogenous brake restraining IFN-I signaling and autoinflammation. Cellular spermine concentration decrease upon stimulations with IFN-I, IL-2, and IL-6. Spermine suppresses phosphorylation of JAK1 in macrophages responding to IFN-I, T cells responding to IL-2, and fibroblasts responding to IL-6. Mechanistically, spermine binds directly to the N-terminal domains of JAK1, resulting in impaired IFNAR2-JAK1 interaction required for initiating downstream signaling and, subsequently, restrained IFN-I effector response. Moreover, spermine attenuates SLE progression in an SLE murine model and reduces IFN-I signaling in PBMCs from SLE patients.

2024-06-21 | GSE192366 | GEO

Cellular spermine targets JAK1 to restrain cytokine-mediated autoimmunity (Human)

Project description:Whole blood samples from SLE patients were collected and PBMCs were isolated using Ficoll-PaqueTM PLUS reagent according to the manufacturer’s protocol. The fresh isolated PBMCs from SLE individuals were treated with DMSO or spermine for 3h, PBMCs from healthy control were used as control, then samples were harvested and lysated with Trizol reagend for RNA-sequencing analysis.

2024-06-21 | GSE223097 | GEO

Cellular spermine targets JAK1 to restrain cytokine-mediated autoimmunity

Project description:Cellular spermine targets JAK1 to restrain cytokine-mediated autoimmunity

| PRJNA905367 | ENA

Cellular spermine targets JAK1 to restrain cytokine-mediated autoimmunity (Mouse)

Project description:Cellular spermine targets JAK1 to restrain cytokine-mediated autoimmunity (Mouse)

| PRJNA923703 | ENA

Cellular spermine targets JAK1 to restrain cytokine-mediated autoimmunity (Human)

Project description:Cellular spermine targets JAK1 to restrain cytokine-mediated autoimmunity (Human)

| PRJNA924822 | ENA

Cellular spermine controls autoinflammation by targeting JAK1 to restrain cytokine response

Project description:Cellular spermine controls autoinflammation by targeting JAK1 to restrain cytokine response

| PRJNA791295 | ENA

DSS/spermine

Project description:Have you tried spermine?

| PRJEB17622 | ENA

Proximal proteins of the type I interferon signaling cascade

Project description:Deciphering the intricate dynamic events governing type I interferon (IFN) signaling is critical to unravel key regulatory mechanisms in host antiviral defense. Here, we leveraged TurboID-based proximity labeling coupled with affinity purification-mass spectrometry to comprehensively map temporal changes to the proximal human proteomes of all seven canonical type I IFN signaling cascade members following IFN stimulation. This established a network of 108 proteins in close proximity to the core members IFNAR1, IFNAR2, JAK1, TYK2, STAT1, STAT2, and IRF9, and validated several known protein assemblies, while also revealing novel, transient associations between key signaling molecules.

2024-05-28 | PXD045482 | Pride

Gene expression profiling upon knockdown of JAK1 in IM9 cells

Project description:Natural Killer (NK) cells are primary effectors of innate immunity directed against transformed cells. In response, tumor cells have developed mechanisms to evade NK cell-mediated lysis but the molecular basis for target cell resistance is not well understood. In the present study, we used a lentiviral shRNA library targeting more than 1000 human genes to identify 83 genes that promote target cell resistance to human NK cells. Many of the genes identified in this genetic screen belong to common signaling pathways, however, none of these genes have previously been known to modulate susceptibility of human tumor cells to immunologic destruction. In particular, gene silencing of two members of the JAK family (JAK1 and JAK2) in a variety of tumor cell targets increased their susceptibility to NK-mediated lysis and induced increased secretion of interferon gamma (IFN-gamma by NK cells. Treatment of tumor cells with JAK inhibitors also induced increased susceptibility to NK cell activity. These findings may have important clinical implications and suggest that small molecule inhibitors of tyrosine kinases being developed as therapeutic anti-tumor agents may also have significant immunologic effects in vivo. IM9 cells were transduced with shRNA-encoding vectors and selected with Puromycin. Two vectors were specifically targeting JAK1 (JAK1-1 and JAK1-3) and one vector encoded an irrelevant control shRNA (CTRL-2). Total RNA was obtained from the parental IM9 cell line, the control-shRNA expressing IM9 cells, the JAK1-1-shRNA and JAK1-3-shRNA expressing IM9 cells in 2 separate experiments (Exp1 and Exp2).

2012-06-27 | E-GEOD-37012 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data