title: 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.
authors.affiliation: Key Laboratory of Infection and Immunity of Chinese Academy of Sciences, Institute of Biophysics Graduate University, Chinese Academy of Sciences, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Luan
authors.forename: J
authors.initials: J
authors.lastname: Ju
authors.forename: L
authors.initials: L
authors.lastname: Luo
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: D-M
authors.initials: DM
authors.lastname: Zhu
authors.forename: L
authors.initials: L
authors.lastname: Cheng
authors.forename: S-Y
authors.initials: SY
authors.lastname: Zhang
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.forename: F-S
authors.initials: FS
authors.lastname: Wang
authors.forename: S
authors.initials: S
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal; D060887:B7 Antigens / Q000097:blood / Q000378:metabolism*; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D006515:Hepatitis B virus / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity*; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000473:pathology*; D022781:Hepatocytes / Q000276:immunology; D006801:Humans; D008099:Liver / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D011993:Recombinant Fusion Proteins; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D060887:B7 Antigens; C423237:CD276 protein, human; D011993:Recombinant Fusion Proteins