Anti-HBV drug entecavir ameliorates DSS-induced colitis through PD-L1 induction

Pharmacol Res. 2022 May:179:105918. doi: 10.1016/j.phrs.2021.105918. Epub 2022 Jan 11.


PD-L1-mediated signaling is one of the major processes that regulate local inflammatory responses in the gut. To date, protective effects against colitis through direct Fc-fused PD-L1 administration or indirect PD-L1 induction by probiotics have been reported. We have previously shown that the anti-HBV drug entecavir (ETV) induces PD-L1 expression in human hepatocytes. In the present study, we investigated whether ETV induces PD-L1 expression in intestinal cells and provides a protective effect against DSS-induced colitis. ETV induced PD-L1 expression in epithelial cells, rather than T and B cells, improving the symptoms of colitis. In the mechanistic analysis, Th17 cell differentiation was inhibited and B cell infiltration into the lamina propria was reduced. In addition, PD-L1 expression was positively correlated with Foxp3 or CSF1-R. In conclusion, ETV upregulated PD-L1 expression in epithelial cells and ameliorated inflammation in DSS-induced colitis. These results suggest that ETV may be a potential therapeutic agent as a PD-L1 enhancer for the treatment of human IBD.

Keywords: CD19 + B cell; Entecavir; PD-L1; Th17 Cell; Treg Cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B7-H1 Antigen* / metabolism
  • Colitis* / chemically induced
  • Colitis* / drug therapy
  • Colitis* / metabolism
  • Dextran Sulfate / pharmacology
  • Guanine / analogs & derivatives
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Pharmaceutical Preparations / metabolism
  • T-Lymphocytes, Regulatory
  • Th17 Cells


  • B7-H1 Antigen
  • Pharmaceutical Preparations
  • entecavir
  • Guanine
  • Dextran Sulfate