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 RNA-sequencing analysis identified several neutrophil chemokines that are elevated in hepatocytes from AH patients, including LECT2 whose role in AH remains largely unknown. AH patients exhibited increased levels of LECT2 in hepatocytes, positively correlating with the severity of AH. Ethanol-fed mice also exhibited elevated liver LECT2, which was abolished
