Characterization of human hepatic natural killer cells in end-stage chronic liver diseases

Hepatic Natural Killer (he-NK) cells are innate immune effectors that contribute to immune tolerance and eliminate dangerous “non-self” antigens. He-NK cells fall into two groups, liver resident (rNK) cells, mainly cytokine secretors, and infiltrating conventional NK (cNK) cells, which are cytotoxic. He-NK cell dysfunction and contribution to end-stage liver disease are not fully understood. The present study evaluates the transcriptomes of he-NK subpopulations in chronic hepatic disease of different etiologies, including sterile inflammation (non-alcoholic steatohepatitis - NASH), autoimmunity (primary sclerosing cholangitis - PSC), and viral infection (hepatitis C - HCV). Overall design: Non-parenchymal cells were isolated from human livers using mechanical and enzymatical dissociation. NK cells (CD56+ CD3-) were FACS sorted and partitioned for scRNAseq using 10x genomics (kit 3' v3.1) technology. Our analysis included cirrhotic livers from NASH (n=4), HCV (n=4), and PSC (n=4) patients and normal livers from healthy donors (n=4).