| First Author | Shimoyama S | Year | 2021 |
| Journal | Eur J Immunol | Volume | 51 |
| Issue | 6 | Pages | 1519-1530 |
| PubMed ID | 33710617 | Mgi Jnum | J:314484 |
| Mgi Id | MGI:6715043 | Doi | 10.1002/eji.202048589 |
| Citation | Shimoyama S, et al. (2021) Ursodeoxycholic acid impairs liver-infiltrating T-cell chemotaxis through IFN-gamma and CX3CL1 production in primary biliary cholangitis. Eur J Immunol 51(6):1519-1530 |
| abstractText | 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. |
