Neutrophils are immobilized at the ductular reaction and promote biliary epithelium expansion in chronic liver injury

Neutrophils play a central role in tissue inflammation. However, their dynamic behavior and function in chronic injury is largely unknow. Here, we show that, in chronic liver injury, neutrophils are recruited to the ductular reaction, where they are immobilized for a prolonged period of time, acquiring an aged phenotype and an altered functionality. Moreover, neutrophils depletion or inhibition of their recruitment reduced ductular reaction expansion, which was found to be NETosis and elastase-dependent. Overall, chronic liver injury alters dthe dynamics, phenotype and function of neutrophils, which promote biliary epithelium expansion and maladaptive wound-healing response. Overall design: Liver and circulating neutrophils from 1 week-treated DDC mice (n=3) were isolated by Ly6G immunomagnetic separation after liver suspension percoll gradient and blood lysis.