Ni Fang, Guo Chuang, Sun Rui, Fu Binqing, Yang Yue, Wu Lele, Ren Sitong, Tian Zhigang, Wei Haiming
1] Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Science and Medical Center, University of Science and Technology of China, 443 Huang-Shan Road, Hefei 230027, China [2] Department of Pathophysiology, Anhui Medical University, 81 Mei-Shan Road, Hefei, Anhui Province 230032, China.
Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Science and Medical Center, University of Science and Technology of China, 443 Huang-Shan Road, Hefei 230027, China.
Sci Rep. 2015 Apr 24;5:9993. doi: 10.1038/srep09993.
Natural killer (NK) cells are critical effectors in the immune response against malignancy and infection, and microRNAs (miRNAs) play important roles in NK cell biology. Here we examined miRNA profiles of human NK cells from different cell compartments (peripheral blood, cord blood, and uterine deciduas) and of NKT and T cells from peripheral blood, and we identified a novel miRNA, miR-362-5p, that is highly expressed in human peripheral blood NK (pNK) cells. We also demonstrated that CYLD, a negative regulator of NF-κB signaling, was a target of miR-362-5p in NK cells. Furthermore, we showed that the over-expression of miR-362-5p enhanced the expression of IFN-γ, perforin, granzyme-B, and CD107a in human primary NK cells, and we found that silencing CYLD with a small interfering RNA (siRNA) mirrored the effect of miR-362-5p over-expression. In contrast, the inhibition of miR-362-5p had the opposite effect in NK cells, which was abrogated by CYLD siRNA, suggesting that miR-362-5p promotes NK-cell function, at least in part, by the down-regulation of CYLD. These results provide a resource for studying the roles of miRNAs in human NK cell biology and contribute to a better understanding of the physiologic significance of miRNAs in the regulation of NK cell function.
自然杀伤（NK）细胞是对抗恶性肿瘤和感染的免疫反应中的关键效应细胞，而微小RNA（miRNA）在NK细胞生物学中发挥着重要作用。在此，我们检测了来自不同细胞区室（外周血、脐带血和子宫蜕膜）的人类NK细胞以及外周血中NKT细胞和T细胞的miRNA谱，并且鉴定出一种新型miRNA，即miR-362-5p，其在人类外周血NK（pNK）细胞中高表达。我们还证明，NF-κB信号的负调节因子CYLD是NK细胞中miR-362-5p的一个靶标。此外，我们表明miR-362-5p的过表达增强了人类原代NK细胞中IFN-γ、穿孔素、颗粒酶B和CD107a的表达，并且我们发现用小干扰RNA（siRNA）沉默CYLD可模拟miR-362-5p过表达的效果。相反，抑制miR-362-5p在NK细胞中产生相反的效果，而CYLD siRNA可消除这种效果，这表明miR-362-5p至少部分地通过下调CYLD来促进NK细胞功能。这些结果为研究miRNA在人类NK细胞生物学中的作用提供了资源，并有助于更好地理解miRNA在调节NK细胞功能中的生理意义。
