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Cellular spermine targets JAK1 to restrain cytokine-mediated autoimmunity

ABSTRACT: Cellular spermine targets JAK1 to restrain cytokine-mediated autoimmunity

PROVIDER: PRJNA905367 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22407841.fastq.gz	Fastqsanger.gz
	SRR22407842.fastq.gz	Fastqsanger.gz
	SRR22407843.fastq.gz	Fastqsanger.gz
	SRR22407844.fastq.gz	Fastqsanger.gz
	SRR22407845.fastq.gz	Fastqsanger.gz

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

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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.

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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.

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