ArticlebioRxiv : the preprint server for biology2026
Neutrophils repurpose the nucleolus as a cytokine reservoir and secretory organelle.
Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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22 authors.
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Abstract
Type I interferons (IFN-I) are critical for antiviral defense but can drive severe pathology when dysregulated. Excess IFN-I is associated with prominent neutrophil accumulation; however, the contribution of neutrophils to IFN-I overproduction remains underexplored. In all cell types previously studied, IFN-I is synthesized de novo following sensing of microbial or host-derived inflammatory stimuli. Contrary to this paradigm, we find that neutrophils express IFNα during development and store it in the nucleolus, a membrane-less intranuclear condensate classically functioning in ribosome biogenesis. TLR-mediated bacterial sensing induces a nucleolar stress response in neutrophils that triggers rapid release of nucleoli-stored IFNα independent of de novo protein synthesis. These findings reveal that neutrophils have repurposed the nucleolus as a cytokine storage and secretory organelle, identify the first naturally occurring immunoregulatory function of nucleolar stress, and provide insight into the relationship between detrimental IFN-I levels and neutrophil accumulation.
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