CD24 regulates Ly6Chi macrophages and BDL-induced liver fibrosis / 中华微生物学和免疫学杂志

ABSTRACT

Objective To investigate the regulatory effects of CD24 on Ly6Chi macrophages in liv-er 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 macro-phages 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 infiltra-tion 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 typeⅠalpha 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 hepat-ic macrophages were significantly elevated in CD24-/-mice compared with those in WT mice. Further analy-sis 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. Mo-reover, 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.