Image_6_Decreased Siglec-9 Expression on Natural Killer Cell Subset Associated With Persistent HBV Replication.TIF Di Zhao Xuemei Jiang Yong Xu Huimin Yang Dongni Gao Xueen Li Lifen Gao Chunhong Ma Xiaohong Liang 10.3389/fimmu.2018.01124.s007 https://frontiersin.figshare.com/articles/figure/Image_6_Decreased_Siglec-9_Expression_on_Natural_Killer_Cell_Subset_Associated_With_Persistent_HBV_Replication_TIF/6388970 <p>Siglec-9 is an MHC-independent inhibitory receptor selectively expressed on CD56<sup>dim</sup> 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<sup>+</sup> 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-β). 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.</p> 2018-05-30 04:12:43 chronic hepatitis B Siglec-9 NK cytokine synthesis cytotoxicity