Decreased Siglec-9 Expression on Natural Killer Cell Subset Associated With Persistent HBV Replication.
Decreased Siglec-9 Expression on Natural Killer Cell Subset Associated With Persistent HBV Replication.
复制标题
与持续 HBV 复制相关的自然杀伤细胞亚群 Siglec-9 表达降低。
DOI：
10.3389/fimmu.2018.01124
复制
发表时间：
2018
影响因子：
7.3
通讯作者：
Liang X
中科院分区：
文献类型：
--
作者：
Zhao D;Jiang X;Xu Y;Yang H;Gao D;Li X;Gao L;Ma C;Liang X
Siglec-9是一种选择性表达于CD56dim NK细胞上的MHC非依赖性抑制性受体。其在感染性疾病中的作用尚未研究。在此，我们研究了NK Siglec-9在慢性B型肝炎（CH B）感染发病机制中的潜在调节作用。流式细胞术评估外周NK细胞上Siglec-9和其他受体的表达。免疫荧光染色用于检测肝活检组织和培养的肝细胞系上的Siglec-9配体。进行Siglec-9阻断试验，并通过流式细胞术检测细胞因子合成和CD107a脱粒。与健康献血员相比，CH B患者的Siglec-9 + NK细胞减少，这与血清B e抗原和HBV DNA滴度密切相关。来自实现持续病毒学应答的患者的NK细胞上的Siglec-9表达恢复至正常供体的水平。Siglec-9的中和恢复了来自CHB患者的NK细胞的细胞因子合成和脱粒。免疫荧光染色显示，在来自CHB患者的肝活检组织中以及在用HBV感染或用炎性细胞因子（IL-6或TGF-β）刺激的肝细胞系中，Siglec-9配体表达增加。这些发现将Siglec-9鉴定为NK细胞的负调节剂，其有助于HBV持续存在，并且Siglec-9信号传导的干预可能具有潜在的翻译意义。
Siglec-9 is an MHC-independent inhibitory receptor selectively expressed on CD56dim 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-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.