The positive feedback loop of furin and TGFβ1 enhances the immune responses of Tregs to hepatocellular carcinoma cells and hepatitis B virus in vitro.

Regulatory T cells (Tregs) can exert immunosuppressive activity. Furin can regulate Treg functions, hepatitis B virus (HBV) persistent infection, and hepatocellular carcinoma (HCC) development. However, it remains unknown whether furin can regulate the immune responses of Tregs to HBV and HCC cells. Here, co-culture systems of HBV1.3P-HepG2 cells and Tregs transduced with or without lentiviral particles that could overexpress furin or knockdown furin/TGFβ1 were established to investigate the regulatory relationship between furin and TGFβ1 and the effect of furin/TGFβ1 on Treg activity. Also, the effects of furin overexpression or furin/TGFβ1 knockdown in Tregs on the immunological activity of effector T cells (Teffs)/cytotoxic T lymphocytes (CTLs) and HBV replication/expression were explored in the co-culture system of Teff/CTL, Treg, and HBV1.3P-HepG2 cells. Our results showed that furin expression and TGFβ1 secretion were notably increased in Tregs, and Furin and TGFβ1 formed a positive feedback loop to activate Tregs in the co-culture system of Tregs and HBV1.3P-HepG2 cells. Furin or TGFβ1 knockdown in Tregs promoted Teff cell proliferation, stimulated IL-2 and IFN-γ secretion, and inhibited HBV replication/gene expression in the co-culture system of Teff, Treg, and HBV1.3P-HepG2 cells. Moreover, furin or TGFβ1 depletion in Tregs enhanced the killing activity of CTLs against HBV1.3P-HepG2 cells and curbed HBV replication/gene expression in the co-culture system of Tregs, CTLs, and HBV1.3P-HepG2 cells. In conclusion, the positive feedback loop of furin and TGFβ1 enhance the immune responses of Tregs to HCC cells and HBV in vitro. This article is protected by copyright. All rights reserved.