Epigenomic profiling of immune cell subtypes reveals H3K27ac-marked stress signatures after long-duration spaceflight

Long-duration spaceflight imposes significant physiological stress on astronauts, including profound alterations in immune function. This study investigated epigenetic changes in immune cells following prolonged orbital spaceflight by analysing histone modifications in CD4+ and CD8+ T-cells from astronauts before, immediately after, and during recovery from spaceflight. Using Cleavage Under Targets and Tagmentation (Cut&Tag) to assess H3K27ac modifications, we identified significant alterations in chromatin accessibility, predominantly involving immune response pathways, gene regulation, and cellular adaptation mechanisms. While some epigenetic changes were transient, others persisted beyond 50 days post-return, suggesting long-term effects. These findings enhance our understanding of immune adaptation to spaceflight and have implications for mitigating spaceflight-associated health risks. Furthermore, they provide valuable insights into immune system regulation under high-stress conditions, potentially informing research on immunodeficiency disorders, cancer epigenetics, and aging-related immune decline on Earth. This study underscores the critical role of epigenetics in long-term space missions and terrestrial health applications.