Spaceflight missions can cause immune system dysfunction in astronauts with little understanding of immune outcomes in deep space. This study assessed immune responses in mice following ground-based, simulated deep spaceflight conditions, compared with data from astronauts on International Space Station missions. For ground studies, we simulated microgravity using the hindlimb unloaded mouse model alone or in combination with acute simulated galactic cosmic rays or solar particle events irradiation. Immune profiling results revealed unique immune diversity following each experimental condition, suggesting each stressor results in distinct circulating immune responses, with clear consequences for deep spaceflight. Circulating plasma microRNA sequence analysis revealed involvement in immune system dysregulation. Furthermore, a large astronaut cohort showed elevated inflammation during low-Earth orbit missions, thereby supporting our simulated ground experiments in mice. Herein, circulating immune biomarkers are defined by distinct deep space irradiation types coupled to simulated microgravity and could be targets for future space health initiatives.

太空飞行任务可能会导致宇航员免疫系统功能障碍，而宇航员对深空的免疫结果知之甚少。这项研究评估了小鼠在地面模拟深空飞行条件下的免疫反应，并与国际空间站任务中宇航员的数据进行了比较。对于地面研究，我们单独使用后肢卸载小鼠模型或结合急性模拟银河宇宙射线或太阳粒子事件辐射来模拟微重力。免疫分析结果揭示了每种实验条件下独特的免疫多样性，表明每种压力源都会导致不同的循环免疫反应，对深空飞行产生明显的影响。循环血浆 microRNA 序列分析揭示了免疫系统失调的参与。此外，大量宇航员在近地轨道任务期间表现出炎症升高，从而支持了我们在小鼠身上进行的模拟地面实验。在此，循环免疫生物标志物是由不同的深空辐射类型与模拟微重力相结合来定义的，并且可能成为未来太空健康计划的目标。