ReferenceID 3097

Ursodeoxycholic acid impairs liver-infiltrating T-cell chemotaxis through IFN-γ and CX3CL1 production in primary biliary cholangitis

Eur J Immunol

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) express

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Reference Id
3097
Evidence Id
19687
Core Evidence Id
19687
Source Reference Id
6190
Herb2 Reference Id
HBREF006987
Subject Paper Key
HBIN047610_33710617
Pubmed Id
33710617
Doi
10.1002/eji.202048589
Paper Title
Ursodeoxycholic acid impairs liver-infiltrating T-cell chemotaxis through IFN-γ and CX3CL1 production in primary biliary cholangitis
Paper Abstract
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.
Journal
Eur J Immunol
Publish Year
2021
Experiment Subject
mouse; human; cell lines; hucc-t1 cells; udca-treated jurkat cells
Experiment Type
Animal & Cell Experiment
Phenotype Related
Primary Biliary Cholangitis
Paper Title Cn
Paper Title En
Ursodeoxycholic acid impairs liver-infiltrating T-cell chemotaxis through IFN-γ and CX3CL1 production in primary biliary cholangitis
Bilingual Status
semi_complete