CD163 impairs HBV clearance in mice by regulating intrahepatic T cell immune response via an IL-10-dependent mechanism.

Background & Aims: Chronic hepatitis B (CHB) arises from a persistent hepatitis B virus (HBV) infection, complicating efforts for a functional cure. Kupffer cells (KCs), liver-resident macrophages, are pivotal in mediating immune tolerance to HBV. Although CD163 marks M2-polarized KCs, its precise role in HBV infection remains unclear and warrants further investigation.

Methods: CD163 expression in liver tissues of patients with CHB was analyzed using the Gene Expression Omnibus (GEO) database. Cd163 knockout mice were utilized to establish HBV-persistent mouse model, and CD163 deficiency effect on HBV viral markers and T cell immune responses were examined in vivo and in vitro.

Results: CD163 expression was elevated and correlated with ALT levels in the liver of patients with CHB. In HBV-persistent mouse model, CD163 deficiency facilitated the clearance of HBsAg, HBeAg, HBV DNA, and HBcAg. Additionally, CD163 deficiency promoted the differentiation of naïve T cells into HBV-specific effector T cells. Further, we found that CD163 deficiency reduces KCs-derived IL-10 secretion, and blocking IL-10 further strengthens the enhanced HBV-specific T cell response due to CD163 deficiency.

Conclusions: Our findings indicate that CD163 deficiency enhances the HBV-specific T cell response, thereby facilitating HBV clearance through reducing KCs-derived IL-10 secretion. This suggests that CD163 may serve as a potential target for the restoration of exhausted T cell function.