失重条件下活化性受体NKG2D对自然杀伤细胞（NK）重力响应的分子调控机制

Space microgravity environment (weightlessness) is associated with immunological alterations, while the decreased cytotoxic activity of natural killer cells has been specially noticed. The cytotoxic activity of NK cells plays a significant role in anti-tumor and anti-virus infection. This cytotoxic activity is finely regulated by the balance of inhibitory receptors and activating receptors on NK cells. Our previous study has confirmed that simulated weightlessness can decrease the cytotoxic activity of human NK cells. Furthermore, we found this modulation resulted from down-regulation of NKG2D receptor, which is an important activating receptor of NK cells. Thus, we present a hypothesis that as the key molecular regulating the activity of NK cells, NKG2D may play an important role in responding to different gravity and immunity decreasing of NK cells..Therefore, we plan to simulate weightlessness by superconducting magnet and stochastic gyroscope to (1) study the effects of simulated weightlessness on mechanical and biological characteristics of NK cells under the molecular-cell level,(2) establish the finite element model of NK cells and analyze the mechanical features of NK cells under simulated weightlessness, (3) study the molecular mechanism of the regulation of NKG2D on NK cells and the related mechanical signal transduction pathway, (4) find out transcriptional factors based on analyzing them obtained from NKG2D promoter of NK cells.Our results will provide experimental data for finely revealing the mechanisms of NKG2D in the process of responding to different gravity of NK cells, and provide a theoretical basis for the study of immune protection measures of astronauts and people of anti-tumor on the ground.

空间失重可导致人体免疫力下降，其中NK细胞活性下降尤为突出。NK是机体抗病毒、抗肿瘤免疫的重要细胞，其活性主要受表面活化性和抑制性受体调控。申请者前期研究证实模拟失重环境下NK细胞活性下降，且发现与其活化性受体NKG2D表达下调密切相关。因此提出，NKG2D作为调控NK细胞活性的关键分子，可能在失重环境下NK细胞对重力响应及免疫功能抑制中发挥重要作用，其表达调控模式在复杂免疫网络中占据重要位置。.本项目拟从特殊环境生物力学角度出发研究:（1）失重对NK细胞力学、生物学特性的影响规律；（2）建立NK细胞有限元模型并分析其失重环境下力学特性；（3）失重环境下NKG2D对NK细胞活性的调控作用及相关力学信号转导通路；（4）在基因表达转录水平明确主导NKG2D表达的启动子序列和转录因子。深入揭示NKG2D在NK细胞重力响应中的作用机理，为空间免疫功能抑制和地面人群抗肿瘤免疫等治疗防护提供理论依据。

空间失重可导致人体免疫力下降，其中NK细胞活性下降尤为突出。NK是机体抗病毒、抗肿瘤免疫的重要细胞，其活性主要受表面活化性和抑制性受体调控。本项目研究证实模拟失重环境下NK细胞活性下降，且发现与其活化性受体NKG2D表达下调密切相关，揭示了NKG2D作为调控NK细胞活性的关键分子在失重环境下NK细胞对重力响应及免疫功能抑制中发挥重要作用，其表达调控模式在复杂免疫网络中占据重要位置。本项目从特殊环境生物力学角度出发研究了:（1）失重对NK细胞力学、生物学特性的影响规律；（2）建立NK细胞有限元模型并分析其失重环境下力学特性；（3）失重环境下NKG2D对NK细胞活性的调控作用及相关力学信号转导通路；（4）在基因表达转录水平明确了主导NKG2D表达的启动子序列和转录因子。研究结果为揭示NKG2D在NK细胞重力响应中的作用机理 、为空间免疫功能抑制和地面人群抗肿瘤免疫等治疗防护提供重要的理论依据。