期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 51, 期 6, 页码 1519-1530出版社
WILEY
DOI: 10.1002/eji.202048589
关键词
CX3CL1; IFN‐ γ liver‐ infiltrating T cells; primary biliary cholangitis; ursodeoxycholic acid
类别
资金
- JSPS KAKENHI [JP26860499]
- National Institutes of Health [DK067003]
The primary treatment for primary biliary cholangitis (PBC), ursodeoxycholic acid (UDCA), works by suppressing the production of IFN-gamma and CX3CL1 to reduce inflammation, ultimately decreasing the chemotactic and adhesive abilities of liver-infiltrating T cells in PBC.
Ursodeoxycholic acid (UDCA) is the primary treatment for primary biliary cholangitis (PBC), but its mechanism of action remains unclear. Studies suggest that UDCA enhances NF erythroid 2-related factor 2 (NFE2L2) expression and that the interaction between IFN-gamma and C-X3-C motif chemokine ligand 1 (CX3CL1) facilitates biliary inflammation in PBC. Therefore, we examined the effects of UDCA on the expression of IFN-gamma and CX3CL1 in in vitro and in vivo PBC models such as human liver tissue, a murine model, cell lines, and isolated human intrahepatic biliary epithelial cells (IHBECs). We observed a significant decrease in IFN-gamma mRNA levels and positive correlations between IFN-gamma and CX3CL1 mRNA levels post-UDCA treatment in PBC livers. NFE2L2-mediated transcriptional activation was significantly enhanced in UDCA-treated Jurkat cells. In 2-octynoic acid-immunized mice, IFN-gamma production by liver-infiltrating T cells was dependent on NFE2L2 activation. IFN-gamma significantly and dose-dependentlyinduced CX3CL1 expression, which was significantly decreased in HuCC-T1 cells and IHBECs upon UDCA treatment. These results suggest that UDCA-induced suppression of IFN-gamma and CX3CL1 production attenuates the chemotactic and adhesive abilities of liver-infiltrating T cells in PBC.
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