Stressed hepatocyte sustains alcohol-associated hepatitis progression by producing leukocyte cell-derived chemotaxin 2

BACKGROUND: Neutrophil infiltration and hepatocyte damage are indispensable hallmarks in alcohol-associated hepatitis (AH), yet the underlying crosstalk between neutrophils and hepatocytes and its role in AH pathogenesis remain unclear. OBJECTIVE: We investigate the regulatory role of leucocyte cell-derived chemotaxin 2 (LECT2) in hepatocyte-neutrophil interaction and its impact on AH progression. DESIGN: We used bulk and single-cell RNA sequencing to identify hepatocyte-secreted factors targeting neutrophils. We analysed serum and liver samples from AH patients and employed genetically modified mice alongside in vitro studies. RESULTS: shRNA ameliorated ethanol-induced liver injury. CONCLUSION: Our studies identified a novel vicious cycle between neutrophils and hepatocytes through the LECT2-PHB2 interaction, presenting a promising therapeutic intervention by targeting LECT2 to mitigate AH in patients.