Integrated single-cell and bulk transcriptomic analyses reveal cDC1-centered ubiquitination dysregulation and identify UBE2F as a critical regulator in sepsis

Background: Sepsis is a life-threatening syndrome with dysregulated immune responses and multiple organ dysfunction. However, precise diagnostic biomarkers and effective therapeutic targets for this syndrome are still lacking. Protein ubiquitination modulates inflammatory regulation and immune cell function, but the specific immune cell subsets that drive ubiquitination-associated immune dysregulation in human sepsis have not been clearly identified. Methods: . Results: experiments showed that silencing UBE2F markedly suppressed dendritic cell activation, decreased proinflammatory cytokine production and organ injury, and ultimately improved survival in septic mice. Conclusions: Our results reveal cDC1 as a key immune cell subset involved in ubiquitination-mediated immune dysregulation in sepsis and suggests that UBE2F may serve as a potential diagnostic biomarker and therapeutic target.