CD24 regulates Ly6Chi macrophages and BDL-induced liver fibrosis

Abstract

Objective To investigate the regulatory effects of CD24 on Ly6Chi macrophages in liver and its influences on bile duct ligation (BDL)-induced hepatic fibrosis in mice. Methods Liver fibrosis was induced in wild-type (WT) and CD24-/- mice by surgical ligation of the biliary duct. Levels of alanine amino transferase (ALT) in serum were detected and liver sections were stained with haematoxylin and eosin (H&E) staining to assess the severity of liver injury. Sirius Red staining was used to observe the degree of liver fibrosis. Real-time PCR was performed for detecting the expression of hepatic fibrosis-related markers and TGF-β1 at mRNA level. The percentage of macrophages and the number of TGF-β1-producing macrophages were measured by flow cytometry. Results BDL-induced liver fibrosis was exacerbated in CD24-/- mice than in WT mice as demonstrated by more serious hyperplasia in bile duct, more inflammatory infiltration at the portal area and higher levels of ALT in serum. Results of Sirius red staining also showed that the liver fibrosis was more severe in CD24-/- mice than in WT mice. Moreover, α-SMA and collagen typeⅠ alpha 1 (Col1a1) were significantly upregulated in CD24-/- mice. Flow cytometry analysis revealed that CD24 was highly expressed by hepatic macrophages in BDL-induced WT mice, and the percentages of hepatic macrophages were significantly elevated in CD24-/- mice compared with those in WT mice. Further analysis revealed that the percentages of Ly6Chi hepatic macrophages in CD24-/- mice were higher than those in WT mice, but there was no significant difference in the percentages of Ly6Clo macrophages. The expression of TGF-β1 at mRNA level was increased in CD24-/- mice as compared with that in WT mice after BDL. Moreover, intracellular staining showed that Ly6Chi hepatic macrophages in CD24-/- mice secreted more TGF-β1 than the macrophages in WT mice. Conclusions CD24 might attenuate the BDL-induced liver fibrosis in mice via regulating the percentage of hepatic Ly6Chi macrophages and the secretion of TGF-β1. Key words: CD24; Bile duct ligation (BDL); Liver fibrosis; Ly6Chi hepatic macrophage; TGF-β1