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Cellular spermine targets JAK1 to restrain cytokine-mediated autoimmunity

GSE218731 Homo sapiens Expression profiling by high throughput sequencing 9 samples Submitted 2024/06/21 Platform GPL28038
Summary
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.
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 PRJNA905367 and SRA study SRP409765. Searching any of these in the dataset finder brings you back here.

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