Fig. 6: Summary of findings.
From: Gut-primed neutrophils activate Kupffer cells to promote hepatic injury in mouse sepsis
During sepsis, neutrophils interact with IELs via CD112 in the gut, resulting in increased NETosis via PAD4-mediated histone citrullination (Cit). NET-forming neutrophils migrate from the gut into the liver and activate PAR-1 on Kupffer cells by NET-contained proteases, such as NE. NET-activated Kupffer cells polarize to an iNOS-expressing M1 phenotype and produce proinflammatory mediators, such as IL-6 and TNF. This gut-liver crosstalk mediated by immune cells leads to sepsis-induced liver injury. PAD4, protein-arginine deiminase type-4; NET, neutrophil extracellular trap; PAR-1, protease-activated receptor-1; NE, neutrophil elastase; iNOS, inducible nitric oxide synthase. Created in BioRender. Murao, A. (2025) https://BioRender.com/fhkfis3.
