HMGB1-mediated formation of IL-33-abundant NETs drives lung-to-kidney injury in severe pneumonia-associated acute kidney injury - PubMed
4 hours ago
- #SP-AKI
- #NETs
- #HMGB1
- Severe pneumonia-associated acute kidney injury (SP-AKI) has a high incidence (53.6%) and mortality (24.2%) in a multicenter cohort.
- Elevated levels of HMGB1, NETs, and IL-33 in circulation are linked to SP-AKI, indicating their role in disease progression.
- HMGB1 in the lungs triggers the formation of NETs that are enriched with IL-33, which then migrate to the kidneys.
- In the kidneys, these NETs activate ST2/NF-κB signaling, leading to inflammation, apoptosis, and kidney injury.
- Interventions targeting HMGB1, IL-33, ST2, or NET formation (via PAD4 inhibition) reduce both lung and kidney damage in models.
- A self-sustaining feed-forward loop exists where HMGB1 amplifies NET-mediated IL-33 release, exacerbating injury.
- NETs are redefined as cross-organ pathogenic carriers, highlighting new therapeutic targets for SP-AKI.