Depletion of Natural Killer Cells improve cholestasis in a murine model of primary biliary cholangitis

Background and Objective: The aim of this study is to investigate the role of NK cells and their phenotypes in xenobiotic induced murine model of primary biliary cholangitis （PBC）by eliminating NK cells. Methods: C57BL/6 female mice were immunized with 2OA-BSA and poly I:C to develop the murine model of PBC. Serologic, histologic, and immunologic testing of PBC mice were analyzed by depleting NK cells with ASGM1 before (ASGM1+PBC group) or after immunization (PBC+ASGM1 group). The proportions of NK cells, CD62L + NK cells, CD4 + , and CD8 + T in liver were analyzed. Results: ALT, AST and ALP in PBC mice was increased. In contrast to PBC mice, AST in ASGM1+PBC group was decreased. Moreover, TBIL was decreased in PBC+ASGM1 group. Notably, ALP and titer of AMA in mice treated with ASGM1 was decreased when compared with PBC mice. Comparing with HC, ASGM1+PBC or PBC+ASGM1 group mice, the ratio of CD4 + T cells in liver declined in PBC mice. In comparison to HC and ASGM1+PBC group mice, the ratio of CD4 + /CD8 + T cells in PBC mice was lower. The frequency of CD62L + NK cells in the liver of PBC mice increased. However, there was no significant difference in histological scores among ASGM1+PBC, PBC+ASGM1 and PBC mice. Conclusions: Eliminating NK cells could reduce the degree of cholestasis and improve the immune imbalance. NK cells were functionally involved in pathogenesis and disease progression, especially CD62L + NK cells in liver might aggravate the progression of PBC.