Astronauts in space… losing gravity, losing immunity?

Introduction

Since the first successful human launch to space on April 12th, 1961, over 600 astronauts have travelled beyond the Earth’s atmosphere. Space travel is essential in driving technological innovation and consistently increases our understanding of the cosmos. However, alongside the thrill of space exploration, astronauts face significant challenges, including profound risks to their immune systems. Astronauts in space endure a unique condition of near weightlessness known as microgravity, which often causes dysregulation of their immune systems.

Effect of microgravity on T-cell immunity

One of the critical studies emphasising the effects of microgravity on the immune system is a twin study conducted by NASA, where they compared various gene expression datasets between an astronaut who had been on the International Space Station (ISS) for one year and their identical twin who had not travelled to space. They discovered changes in the methylation patterns of immunologically relevant genes such as NOTCH3 and SLC1A5, which are both crucial in T cell development. They also found microgravity caused an increase in pro-inflammatory molecules and decreased anti-inflammatory molecules, alluding to spaceflight causing an increased inflammatory state. These patterns are consistent with other experiments simulating microgravity conditions, such as prolonged bed rest models.

Microgravity has also been shown to induce thymic atrophy, which is when the thymus slowly shrinks and loses its function. The thymus is a primary lymphoid organ that is crucial in T cell development. An experiment performed on the International Space Station (ISS) has shown that exposing mice to 1g gravity can alleviate microgravity-induced thymic atrophy (Figure 1), suggesting that exposure to a standard gravitational field is a potential treatment. The thymic environment is altered due to microgravity. In particular, thymic epithelial cells (TECs) are misplaced and, therefore cannot perform their role in T cell maturation. Overall, there is a significant decrease in the output of T cells from the thymus, shown by a clear decrease in thymic mass and alterations in gene expression related directly to the process of T cell differentiation.

Effect of microgravity on the bone marrow

Furthermore, microgravity affects the bone marrow, another primary lymphoid organ. The bone marrow consists of many mesenchymal stem cells (MSCs), which differentiate hematopoietic stem cells (HSCs) into leukocytes. Microgravity inhibits osteogenesis and promotes adipogenesis, which means that bone formation is slowed down, but fat cell production is increased. This happens due to the changes to the structure inside the

cell, known as actin cytoskeleton, which affects transcriptional regulators, which generally control cell differentiation. In space, there is also suppression of the cytokine CXCL2 in MSCs, which affects HSC differentiation into immune cells, indicating a link between MSC dysfunction and immunosuppression faced by astronauts.

Other factors affecting the immune system

Microgravity is the main factor behind immune system dysregulation in astronauts, but other factors, such as stress and exposure to cosmic radiation, also play a role. Cosmic radiation can damage DNA, leading to mutations that impair the immune system’s ability to function properly. Stress hormones are known to affect immune system function. For instance, cortisol can reduce the number of leukocytes in circulation.

Conclusion

Due to the compromised state of the astronauts’ immune systems, latent viruses often reactivate. Herpes viruses, such as varicella-zoster virus (chickenpox!) and Epstein-Barr virus, have been documented to be reactivated in astronauts during and after space flight. This is mainly due to the loss of T cell immunity (Figure 2) and a reduction in NK cell potency and number. Microgravity affects NK cells by changing their cytoskeletal

form, which they need to perform cytotoxic functions.

Understanding and mitigating the risks of space travel is crucial as more prolonged and ambitious missions are planned, such as sending humans to Mars. The primary medical countermeasure for the reactivation of herpes viruses is re-vaccination. However, at this current point, only a vaccine for varicella-zoster virus is available. Future research focusing on artificial gravity and environmental changes on spacecraft and the ISS may provide a safer journey for astronauts spending extended time in space.

Written by Devanshi Shah

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REFERENCES

Akiyama, T., Horie, K., Hinoi, E., Hiraiwa, M., Kato, A., Maekawa, Y., Takahashi, A. & Furukawa, S. (2020) How does spaceflight affect the acquired immune system? npj Microgravity. 6 (1), 1–7. doi:10.1038/s41526-020-0104-1.

Simon N. Archer, Carla Möller-Levet, María-Ángeles Bonmatí-Carrión, Emma E. Laing, Derk-Jan Dijk. Extensive dynamic changes in the human transcriptome and its circadian organization during prolonged bed rest -ScienceDirect. https://www-sciencedirect-

com.iclibezp1.cc.ic.ac.uk/science/article/pii/S2589004224005522?via%3Dihub [Accessed: 16 August 2024].

Hicks J, Olson M, Mitchell C, Juran CM, Paul AM. The Impact of Microgravity on Immunological States. Immunohorizons. 2023 Oct 1;7(10):670-682. doi: 10.4049/immunohorizons.2200063. PMID: 37855736; PMCID: PMC10615652.

The NASA Twins Study: A multidimensional analysis of a year-long human spaceflight | Science. https://www.science.org/doi/10.1126/science.aau8650 [Accessed: 16 August 2024].

Hicks, J., Olson, M., Mitchell, C., Juran, C.M. & Paul, A.M. (2023) The Impact of Microgravity on Immunological States. ImmunoHorizons. 7 (10), 670–682. doi:10.4049/immunohorizons.2200063.

Hobbs, Z. (2023) How many people have gone to space? | Astronomy.com. Astronomy Magazine. https://www.astronomy.com/space-exploration/how-many-people-have-gone-to-space/.

Mehta, S.K., Laudenslager, M.L., Stowe, R.P., Crucian, B.E., Feiveson, A.H., Sams, C.F. & Pierson, D.L. (2017) Latent virus reactivation in astronauts on the international space station. npj Microgravity. 3 (1), 1–8. doi:10.1038/s41526-017-0015-y.

Surrey, U. Microgravity found to cause marked changes in gene expression rhythms in humans. https://phys.org/news/2024-03-microgravity-gene-rhythms-humans.html [Accessed: 16 August 2024].