Decreased siglec-9 expression on natural Killer cell subset associated With Persistent hBV replication

作者：Zhao, Di; Jiang, Xuemei; Xu, Yong; Yang, Huimin; Gao, Dongni; Li, Xueen; Gao, Lifen; Ma, Chunhong^*; Liang, Xiaohong^*

来源：Frontiers in Immunology, 2018, 9: 1124.

DOI：10.3389/fimmu.2018.01124

• chronic hepatitis B
• Siglec-9
• NK
• cytokine synthesis
• cytotoxicity

Siglec-9 is an MHC-independent inhibitory receptor selectively expressed on CD56(dim) NK cells. Its role in infection diseases has not been investigated yet. Here, we studied the potential regulatory roles of NK Siglec-9 in the pathogenesis of chronic hepatitis B (CHB) infection. Flow cytometry evaluated the expression of Siglec-9 and other receptors on peripheral NK cells. Immunofluorescence staining was used to detect Siglec-9 ligands on liver biopsy tissues and cultured hepatocyte cell lines. Siglec-9 blocking assay was carried out and cytokine synthesis and CD107a degranulation was detected by flow cytometry. Compared to healthy donors, CHB patients had decreased Siglec-9(+) NK cells, which reversely correlated with serum hepatitis B e antigen and HBV DNA titer. Siglec-9 expression on NK cells from patients achieving sustained virological response recovered to the level of normal donors. Neutralization of Siglec-9 restored cytokine synthesis and degranulation of NK cells from CHB patients. Immunofluorescence staining showed increased expression of Siglec-9 ligands in liver biopsy tissues from CHB patients and in hepatocyte cell lines infected with HBV or stimulated with inflammatory cytokines (IL-6 or TGF-beta). These findings identify Siglec-9 as a negative regulator for NK cells contributing to HBV persistence and the intervention of Siglec-9 signaling might be of potentially translational significance.

• 出版日期2018-5-30
• 单位山东大学