With dwindling natural resources on earth, current and future generations will need to explore space to new planets that will require travel under no or varying gravity conditions. Hence, long-term space missions and anticipated impacts on human biology such as changes in immune function are of growing research interest. Here, we reported new findings on mechanisms of immune response to microgravity with a focus on macrophage as a cellular model. We employed a superconducting magnet to generate a simulated microgravity environment and evaluated the effects of simulated microgravity on RAW 264.7 mouse macrophage cell line in three time frames: 8, 24, and 48 h. As study endpoints, we measured cell viability, phagocytosis, and used next-generation sequencing to explore its changing mechanism. Macrophage cell viability and phagocytosis both showed a marked decrease under microgravity. The differentially expressed genes (DEG) were identified in two ways: (1) gravity-dependent DEG, compared μg samples and 1 g samples at each time point; (2) time-dependent DEG, compared time-point samples within the same gravitational field. Through transcriptome analysis and confirmed by molecular biological verification, our findings firstly suggest that microgravity might affect macrophage phagocytosis by targeting Arp2/3 complex involved cytoskeleton synthesis and causing macrophage immune dysfunction. Our findings contribute to an emerging body of scholarship on biological effects of space travel.

随着地球上自然资源的不断减少，当代人和子孙后代将需要探索太空到新的行星，这需要在无重力或变化的重力条件下旅行。因此，长期太空任务和对人类生物学的预期影响（例如免疫功能的变化）引起了越来越多的研究兴趣。在这里，我们报告了关于微重力免疫反应机制的新发现，重点关注巨噬细胞作为细胞模型。我们采用超导磁体生成模拟微重力环境，并评估模拟微重力在 8、24 和 48 小时三个时间范围内对 RAW 264.7 小鼠巨噬细胞系的影响。作为研究终点，我们测量了细胞活力、吞噬作用，并使用新一代测序来探索其变化机制。微重力下巨噬细胞活力和吞噬能力均显着下降。差异表达基因（DEG）的鉴定有两种方式：（1）重力依赖性DEG，比较每个时间点的μg样品和1g样品； (2)时间相关DEG，比较同一引力场内的时间点样本。通过转录组分析和分子生物学验证，我们的研究结果首先表明微重力可能通过靶向参与细胞骨架合成的Arp2/3复合物影响巨噬细胞的吞噬作用，导致巨噬细胞免疫功能障碍。我们的发现有助于建立关于太空旅行生物效应的新兴学术机构。