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Cellular spermine targets JAK1 to restrain cytokine-mediated autoimmunity

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): Homo sapiens

PROVIDER: GSE218731 | GEO | 2024/06/21

REPOSITORIES: GEO

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