JNK2可增强NKG2D介导的自然杀伤细胞肿瘤杀伤效应

JNK2 enhances the NKG2D-mediated natural killer cell cytotoxicity

目的：探讨c-Jun氨基末端激酶2（c-Jun N-terminal kinase，JNK2）信号通路对自然杀伤（ NK）细胞肿瘤杀伤效应的影响。方法采用Western blot检测活化淋巴细胞中JNK信号及其上游激酶的磷酸化情况；采用体外杀伤试验和流式细胞技术检测JNK2缺失对NKG2D （ natural-killer group 2 member D）介导的NK细胞效应细胞因子产生及肿瘤杀伤的影响；利用JNK2基因敲除小鼠构建移植瘤模型，对其皮下肿瘤生长情况进行观察和检测，并与野生型小鼠进行比较。结果淋巴细胞早期活化伴随着JNK及其上游激酶的活化。肿瘤细胞表达的高亲和力NKG2D配体可显著增强NK细胞对肿瘤细胞的杀伤作用。当JNK2信号通路缺失后，经NKG2D介导的NK细胞效应细胞因子产生及肿瘤清除的能力均显著减弱，进而导致机体肿瘤控制能力减弱。结论 JNK2信号通路对由NKG2D 介导的NK细胞活化、NK细胞的肿瘤清除和免疫监视能力具有重要的调节作用。

Objective To investigate the effects of c-Jun N-terminal kinase （JNK） 2 on NKG2D-mediated natural killer （ NK） cell cytotoxicity .Me thods NK cells were activated by polyinosinic-polycyti-dylic acid （ Poly I∶C ） .The activation status of JNK signaling pathway was detected .The cytotoxicity of ac-tivated NK cells and the level of IFN-γproduced were measured to determine the function of NK cells in the absence of JNK2.Tumor growth in wild type and JNK2-knockout （JNK2-/-） mice with lymphoma xenograft were measured to evaluate immune surveillance of NK cells .Results The phosphorylation of JNK and up-stream kinases were observed in the early stage of cell activation after treatment of Poly I ∶C.The expressed ligands of the activating receptors NKG2 D significantly increased NK cell cytotoxicity to lymphoma cells . JNK2 deficiency impaired the antitumor effects of NK cells , and then resulted in enhanced tumor growth in JNK2-/-mice.Conclusion JNK2 signaling pathway is involved in the NKG2 D-mediated activation of NK cells and regulates immune surveillance of NK cells against tumor .