穿孔素
NKG2D公司
颗粒酶B
生物
淋巴因子激活杀伤细胞
颗粒酶
自然杀伤细胞
白细胞介素21
提吉特
癌症研究
免疫学
肿瘤坏死因子α
白细胞介素12
基因沉默
免疫系统
细胞毒性T细胞
T细胞
CD8型
体外
基因
生物化学
作者
Jiantao Han,Chao Ke,Bin Jiang,Hongjian Zhou,Hanbin Xu,Xingwang Xie
摘要
Hepatocellular carcinoma (HCC) is the world's leading cause of tumor-related mortalities. Natural killer (NK) cells play a critical role at the first immunological defense line against HCC initiation and progression. NK cell dysfunction is therefore an important mechanism for immune evasion of HCC cells. In the present study using a murine HCC model, we revealed the down-regulation of PR/SET Domain 10 (PRDM10) in hepatic NK cells that were phenotypically and functionally exhausted. PRDM10 silencing diminished the expression of natural killer group 2 member D (NKG2D) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), augmented T cell immunoglobulin and ITIM domain (TIGIT) expression, and decreased the expression of interferon (IFN)-γ, perforin and granzyme B in normal hepatic NK cells in vitro. Consistently, PRDM10-deficient NK cells exhibited impaired cytotoxicity on target cells. In contrast, PRDM10 over-expression promoted NKG2D and Fas ligand (FasL) expression, reduced CD96 expression and enhanced transcripts of IFN-γ, perforin and granzyme B in NK cells in vivo. Moreover, PRDM10 silencing and PRDM10 over-expression down-regulated and up-regulated Eomesodermin (Eomes) expression, respectively. In summary, this study reveals PRDM10 down-regulation as a novel mechanism underlying NK cell dysfunction and identifies PRDM10 as a supporting factor of NK cell function.
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