Potential role of soluble B7‐H3 in liver immunopathogenesis during chronic HBV infection

Abstract

Immune-mediated mechanisms have been implicated in liver pathogenesis and subsequent progression in hepatitis B virus (HBV) infection. Costimulatory molecules, the important regulators of immune responses, participate in the regulation of liver pathology in HBV infection. However, the role of B7-H3 (CD276, a new member of B7 family) in this process has not been investigated. In this study, we detected abundant soluble B7-H3 (sB7-H3) in the plasma of patients with chronic HBV infections. The increase of the plasma B7-H3 was associated with the progression of liver cirrhosis and accompanied by decreased expression of B7-H3 on hepatocytes. The identification analysis suggests that the plasma B7-H3 might be derived from the membrane-bound B7-H3 on hepatocytes. A functional study showed that immobilized (4Ig) B7-H3Ig fusion protein could inhibit TCR-induced proliferation and IFN-γ secretion of T cells, which could be partially blocked by soluble B7-H3flag fusion protein. These results suggest that the reduced expression of B7-H3 in the livers might temper the inhibition of T-cell responses mediated by B7-H3 expressed on hepatocytes and thus promote the hepatic inflammation and hepatitis progression in the chronic HBV-infected patients.