Liver infiltration of multiple immune cells during the process of acute liver injury and repair

Background: Immune cells, including neutrophils, natural killer (NK) cells, T cells, NKT cells and macrophages, participate in the progression of acute liver injury and hepatic recovery. To date, there has been no systematic study on the quantitative changes in these different immune cells from initial injury to subsequent recovery.

Aim: To investigate the infiltration changes of various immune cells in acute liver injury models over time, and to study the relationship between the changes in leukocyte cell-derived chemotaxin 2 (LECT2) and the infiltration of several immune cells.

Methods: Carbon tetrachloride- and concanavalin A-induced acute liver injury models were employed to mimic toxin-induced and autoimmune-mediated liver injury respectively. The quantitative changes in various immune cells were monitored at different time points. Serum samples were collected, and liver tissues were harvested. Ly6G, CD161, CD4, CD8 and F4/80 staining were used to indicate neutrophils, NK/NKT cells, CD4⁺ T cells, CD8⁺ T cells and macrophages, respectively. Lect2-KO mice were used to detect the function of LECT2.

Results: During the injury and repair process, different types of immune cells began to increase, reached their peaks and fell into decline at different time points. Furthermore, when the serum alanine transaminase (ALT) and aspartate transaminase (AST) indices reverted to normal levels 7 d after the injury, the infiltration of immune cells still existed even 14 d after the injury, showing an obvious lag effect. We found that the expression of LECT2 was upregulated in acute liver injury mouse models, and the liver injuries of Lect2-KO mice were less severe than those of wild-type mice. Compared with wild-type mice, Lect2-KO mice had different immune cell infiltration.

Conclusion: The recovery time of immune cells was far behind that of serum ALT and AST during the process of liver repair. LECT2 could regulate monocyte/macrophage chemotaxis and might be used as a therapeutic target for acute liver injury.