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Abstract
Integration of multi-cohort transcriptomic and single-cell datasets shows that circadian gene dysregulation in patients with sepsis correlates with disease severity and immunosuppressive states.
- Circadian disruption is observed in patients with sepsis, indicating a potential link between circadian rhythms and immune function.
- Monocytes and macrophages are identified as key immune cells affected by circadian gene dysregulation in sepsis.
- Elevated levels of the core clock repressor NR1D1 in macrophages suppress the transcription of the Igf2bp2 gene, contributing to immunosuppression.
- Loss of IGF2BP2 destabilizes specific transcripts, leading to impaired phagolysosomal acidification rhythms and reduced pathogen clearance.
- Knocking down NR1D1 restores IGF2BP2 expression and phagolysosomal function, suggesting a potential therapeutic target.
- Engineered hybrid membrane nanovesicles that deliver siRNA against NR1D1 improve immune function and survival in septic mice.
Simplified
Circadian Biology