KCTD9 contributes to liver injury through NK cell activation during hepatitis B virus-induced acute-on-chronic liver failure

Abstract We explored the expression of a newly identified potassium channel tetramerisation domain containing 9 (KCTD9) protein in 113 blood and 81 liver samples, from patients with mild chronic hepatitis B (CHB) or HBV-induced acute-on-chronic liver failure (HBV-ACLF). KCTD9 was highly expressed in peripheral and hepatic NK cells from HBV-ACLF patients compared with mild CHB patients, and this correlated positively with the severity of liver injury. The role of KCTD9 was further investigated in NK92 cells in vitro. KCTD9 overexpressed NK92 cells exhibited a marked increase in CD69 expression, cytotoxicity, IFN-γ secretion and a significant decrease in NKG2A receptor expression. Inhibition of KCTD9 by shRNA resulted in reduced cytotoxic function. These results suggest the involvement of KCTD9 in NK cell activation and provide additional insight into a potential therapeutic target for molecular manipulation for HBV-ACLF patients.