Beyond Low-Earth Orbit: Characterizing the Immune Profile Following Simulated Spaceflight Conditions for Deep Space Missions

Spaceflight missions can cause immune system dysfunction in astronauts with little understanding of immune outcomes in deep space. This study assessed immune responses following ground-based, simulated deep spaceflight conditions, compared to data from astronauts on ISS 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 involvment in immune system dysregulation. Furthermore, a large astronaut cohort showed elevated inflammation during LEO missions, thereby supporting our simulated ground experiments. 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.