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

• Published in: Pharmacological research Vol. 179; p. 105918
• Main Authors: Yamamoto, Yuichiro, Carreras, Joaquim, Shimizu, Takanobu, Kakizaki, Masatoshi, Kikuti, Yara Yukie, Roncador, Giovanna, Nakamura, Naoya, Kotani, Ai
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.05.2022
• Subjects: CD19 + B cell; Entecavir; PD-L1; Th17 Cell; Treg Cell; GALT; FFPET; LP; IHC; ETV; HRP; Entecavir; IBD; IL-22; SLE; MFI; S1P; Th17 Cell; Treg Cell; PD-L1; HBV; NRTI; Th17; CD; GI; DSS; CD19 + B cell; CSF1-R; H&E; Treg; IL-10; TNF-α; JAK; mAbs; TGF-β1; Foxp3; PD-1; HDAC
• ISSN: 1043-6618; 1096-1186; 1096-1186
• DOI: 10.1016/j.phrs.2021.105918

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. [Display omitted]