Â鶹ÒùÔº

With the advent of commercial spaceflight, an increasing number of people may be heading into space in the coming years. Some will even get a chance to fly to the moon or live on Mars.

One of the major health risks associated with spaceflight involves the immune system, which normally fights off viruses and cancer. It's already established that spaceflight weakens immunity; current and past astronauts report clinical issues such as respiratory illnesses and skin rashes. These issues may become even more serious on longer-term flights, such as to Mars.

To better understand the full scope of immunology during spaceflight, Buck Associate Professor Dan Winer, MD, working with colleagues linked to the National Aeronautics and Space Administration (NASA), the European Space Agency (ESA), Cornell University, the University of Pittsburgh, the University of Toronto, Embry-Riddle Aeronautical University, and others, have put together a comprehensive guide describing a full array of science linking spaceflight and the immune system.

Given the large, rapidly expanding knowledge base on the topic, the team used the name "astroimmunology" to define a subdiscipline of immunology dedicated to the study of the effects of spaceflight and its associated stressors on the immune system. The work is published in Nature Reviews Immunology.

"The future of humanity will involve living in outer space or on distant worlds for some people. The larger goal of establishing this emerging subspecialty of astroimmunology is to develop countermeasures to protect the health of those exploring life off of Earth," says Winer.

"What's special about this paper is that we provide integrated mechanistic insights into how all of these space-related stressors interface to alter immune physiology, and by doing so, we have defined the scope of an entire field, for the most part, in a single paper. As a bonus, many of these mechanisms may also have relevance in aging research."

The stressors of spaceflight

The guide begins by describing how spaceflight stressors, including microgravity, cosmic radiation, changes in sleep-wake patterns and physiological stress (from mission-associated variables), are studied on Earth to mimic spaceflight, and what we have learned from these studies, paying special attention to the biological mechanisms by which these stressors adversely affect immune function.

Next, the authors discuss how spaceflight immune crosstalk changes the microbiome of space travelers and facilitates reactivation of latent viruses. The authors then focus their discussion on summarizing how the immune system changes during and after actual spaceflight, harnessing findings from recent missions on the International Space Station, the NASA Twins' study, and the SpaceX Inspiration 4 mission.

Their discussion integrates data from contemporary multiomic analyses from these studies, providing comprehensive and modern insights into up-to-date mechanisms by which spaceflight adversely impacts immunity.

"Most of the classical human immunology data on spaceflight came from basic phenotyping studies—you could see that spaceflight perturbed the immune system, but there was very little known on why the immune system didn't function well in space," says Winer, who currently has multiple space-related projects going in his lab.

"Now that investigators have brought multiomics into the work, we and others are able to identify mechanisms and hallmarks of space-related immune dysfunction."

The paper then defines clinical risks of immune dysfunction in space, and defines avenues for countermeasures, including immune monitoring, the development of an immune countermeasure protocol, vaccinations, and the use of machine learning to predict space nutraceuticals.

The work is informed by research published by the Winer lab last year in Nature Communications providing the first single-cell atlas of the human immune system in simulated microgravity with spaceflight validation, and the identification of space nutraceutical countermeasures, such as quercetin, that could be used to normalize immunity during space travel.

Finally, the authors look forward to new space stations, the moon, and Mars, discussing issues surrounding biobanking approaches to study the immune system in space, including the Cornell Aerospace Medicine Biobank (CAMBank). The authors also highlight challenges inherent to living on Mars, such as how variable gravity, increased radiation and lunar or Martian dust could impact immune cell function over time.

"We can now track precisely how each cell of the immune system adapts to space and varied planetary environments, which can guide preparations for new missions and help keep astronauts safe," Christopher Mason, Ph.D., the WorldQuant Professor of Genomics and Computational Biomedicine at Weill Cornell Medicine.

"The study of astroimmunology is still in a very early stage," says Winer, who notes that more astronaut data will be coming soon from the field. "We think this paper sets the stage as a guide for future research in one of the body's systems most impacted by spaceflight. It certainly is an exciting time to be involved in space research."

Implications for aging research

The paper also highlights parallels between the impact of spaceflight and aging on the immune system, suggesting synergistic benefits to both fields of study. Huixun Du, a recent Ph.D. graduate from the Winer lab, is a lead author of the study.

"Spaceflight is an excellent model for accelerated aging," she says, adding that researchers can now see the details of how mitochondria fail in space. "Mitochondria don't work as efficiently in space and start producing free radicals. These same processes happen with aging."

Du is particularly excited about work that shows the cytoskeleton, which gives cells shape and coherence, becomes disorganized in microgravity.

"What if that same disorganization happens in aging?" she asks. "Studying this phenomenon in space could jumpstart efforts aimed at keeping our cells healthy as we age."