Gao Ming, Yang Yan, Li Daling, Ming Bingxia, Chen Huoying, Sun Yan, Xiao Yifan, Lai Lin, Zou Huijuan, Xu Yong, Xiong Ping, Tan Zheng, Gong Feili, Zheng Fang
Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Division of Viral Pathology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
Innate Immun. 2016 Aug;22(6):395-404. doi: 10.1177/1753425916658111. Epub 2016 Jul 1.
NK cells participate in the development of human multiple sclerosis (MS) and mouse experimental autoimmune encephalomyelitis (EAE), but the roles of different NK cell subsets in disease onset remain poorly understood. In this study, murine NK cells were divided into CD27(high) and CD27(low/-) subsets. The CD27(high) subset was decreased and the CD27(low/-) subset was increased in lymphoid organs during the pre-onset stage of EAE. Compared with the counterpart in naïve mice, the CD27(high) subset showed lower expression of Ly49D, Ly49H and NKG2D, and less production of IFN-γ, whereas the CD27(low/-) subset showed similar expression of the above mentioned surface receptors but higher cytotoxic activity in EAE mice. Compared with the CD27(high) subset, the CD27(low/-) subset exhibited increased promotion of DC maturation and no significant inhibition of T cells proliferation and Th17 cells differentiation in vitro Additionally, adoptive transfer of the CD27(low/-) subset, but not the CD27(high) subset, exacerbated the severity of EAE. Collectively, our data suggest the CD27 NK cell subsets play different roles in controlling EAE onset, which provide a new understanding for the regulation of NK cell subsets in early autoimmune disease.
自然杀伤（NK）细胞参与人类多发性硬化症（MS）和小鼠实验性自身免疫性脑脊髓炎（EAE）的发病过程，但不同NK细胞亚群在疾病发病中的作用仍知之甚少。在本研究中，将小鼠NK细胞分为CD27高表达和CD27低表达/阴性亚群。在EAE发病前期，淋巴器官中CD27高表达亚群减少，CD27低表达/阴性亚群增加。与未免疫小鼠的对应亚群相比，CD27高表达亚群的Ly49D、Ly49H和NKG2D表达较低，干扰素-γ产生较少，而CD27低表达/阴性亚群在EAE小鼠中上述表面受体表达相似，但细胞毒性活性较高。与CD27高表达亚群相比，CD27低表达/阴性亚群在体外对树突状细胞（DC）成熟的促进作用增强，对T细胞增殖和Th17细胞分化无明显抑制作用。此外，过继转移CD27低表达/阴性亚群而非CD27高表达亚群会加重EAE的严重程度。总体而言，我们的数据表明CD27 NK细胞亚群在控制EAE发病中发挥不同作用，这为自身免疫性疾病早期NK细胞亚群的调控提供了新的认识。
