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Cellular spermine controls autoinflammation by targeting JAK1 to restrain cytokine response

GSE192366 Mus musculus Expression profiling by high throughput sequencing 8 samples Submitted 2024/06/21 Platform GPL24247
Summary
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.
Published in
Cellular spermine targets JAK signaling to restrain cytokine-mediated autoimmunity
Xu H, Zhang X, Wang X et al. · Immunity 2024 · PMID 38908373 · doi:10.1016/j.immuni.2024.05.025
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Also filed as BioProject PRJNA791295 and SRA study SRP351894. Searching any of these in the dataset finder brings you back here.

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