Beyond Low-Earth Orbit: Characterizing Immune and microRNA Differentials following Simulated Deep Spaceflight Conditions in Mice

Amber M Paul; Margareth Cheng-Campbell; Elizabeth A Blaber; Sulekha Anand; Sharmila Bhattacharya; Sara R Zwart; Brian E Crucian; Scott M Smith; Robert Meller; Peter Grabham; Afshin Beheshti

doi:10.1016/j.isci.2020.101747

Beyond Low-Earth Orbit: Characterizing Immune and microRNA Differentials following Simulated Deep Spaceflight Conditions in Mice

iScience. 2020 Nov 25;23(12):101747. doi: 10.1016/j.isci.2020.101747. eCollection 2020 Dec 18.

Authors

Amber M Paul^{1

2}, Margareth Cheng-Campbell³, Elizabeth A Blaber^{2

3}, Sulekha Anand⁴, Sharmila Bhattacharya², Sara R Zwart⁵, Brian E Crucian⁶, Scott M Smith⁶, Robert Meller⁷, Peter Grabham⁸, Afshin Beheshti⁹

Affiliations

¹ Universities Space Research Association, Columbia, MD 21046, USA.
² Space Biosciences Division, NASA Ames Research Center, Moffett Field, CA 94043, USA.
³ Department of Biomedical Engineering, Center for Biotechnology & Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
⁴ Department of Biological Sciences, San Jose State University, San Jose, CA 95112, USA.
⁵ Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston, TX 77555, USA.
⁶ NASA Johnson Space Center, Houston, TX 77058, USA.
⁷ Department of Neurobiology/Pharmacology, Morehouse School of Medicine, Atlanta, GA 30310, USA.
⁸ Center for Radiological Research, Columbia University, New York, NY 10027, USA.
⁹ KBR, Space Biosciences Division, NASA Ames Research Center, Moffett Field, CA 94043, USA.

Abstract

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.

Keywords: Immunology; Space Sciences.