• Since the Apollo missions started almost 60 years ago, scientists have been monitoring space travel’s negative effects on health.
• A new study concludes that reduced gravity makes the immune system malfunction, reducing the immune response.
• This study could pave the way for developing methods that reduce immune system impairment during long-term space exploration.

Dr. Millie Hughes-Fulford was one of the first female astronauts. Until her death in February 2021, she led a team of researchers at University of California, San Francisco (UCSF) and Stanford University in investigating the role of regulatory T cells (Tregs) in immune system dysfunction during space travel.

The lead author of the new study is Dr. Jordan Spatz, a postdoctoral fellow and space scientist at UCSF, and the senior author is Dr. Brice Gaudilliere, an associate professor in the Department of Anesthesia at the Stanford University School of Medicine.

The study appears in the latest edition of Scientific Reports.

Alarming observations

Space scientists know that exposure to microgravity, or weak gravity, can wreak havoc on human health.

The Apollo astronauts experienced a number of illnesses upon their return to Earth. More than half of them caught colds or other infections within 1 week of completing their journeys.

Some astronauts dealt with inner ear disturbances, low blood pressure, arrhythmia, and reactivation of the chickenpox virus. Some also lost bone calcium or were dehydrated.

These findings inspired probes into the effects of microgravity on the immune system.

Over the past 6 decades, scientists have led such inquiries during rocket launches, shuttle trips, space station terms, and earthbound laboratory space gravity simulations.

Tregs turn rogue in space

Tregs play a vital role in regulating many types of immune responses. Often, these cells dampen the immune responses as an infection subsides.

They are involved in a number of processes, including oral tolerance, which is “the active process by which the immune system does not respond to an orally administered antigen,” such as food. Tregs also play a role in resistance to infections, allergy sensitivities, immune memory, and transplantation tolerance, in which the immune system does not attack transplanted tissue.

The current study’s findings indicate that space travel activates Tregs earlier, thereby damping down the immune system before the threat has been cleared.

Unexpected results

The scientists exposed blood samples from eight healthy adult participants to simulated microgravity.

They loaded the samples into a machine developed by the National Aeronautics and Space Administration (NASA), called the Rotating Wall Vessel, exposing the samples to 18 hours of either 1-gravity, which is the amount of gravity experienced on Earth, or microgravity.

Using a novel single-cell analysis, the researchers could pinpoint individual immune cells by type in order to detect and tally proteins involved in immune function.

This study offers greater insight into the cellular interactions that explain microgravity’s immunosuppressive effects.

According to the researchers, the lack of gravity seems to set off a multicellular response that may lower resistance to pathogens.

Surprisingly, when the team stimulated an immune response in the blood samples with two molecules that mimicked a pathogen, the Tregs dampened the resulting immune response before it had time to respond to the threat.

The study authors report: “Our data indicate that exposure to [microgravity] results in the broad inhibition of immune cell capacity to respond to a potent activating stimulus […] and are consistent with transcriptomic previous analyses of human immune cells exposed to the spaceflight environment.”

Dr. Gaudilliere calls this a “double whammy” of “a dampening of T lymphocyte immune activation responses — but also an exacerbation of immunosuppressive responses by Tregs.” T lymphocytes, which are also called T cells, play a central role in the body’s response to pathogens. Under microgravity, T cells are less responsive. However, antibody-producing B cells were not affected in the same way.

Certain limitations

The study’s authors mention several limitations. They stress that using a microgravity simulation model makes it hard to generalize the findings. However, they argue that this cost-effective experimentation can identify novel biological effects that can later be tested in-flight.

Also, the study’s design concentrated on one time point of exposure to low gravity. The team feels that future investigations with additional time points “are warranted and should be high priority.”

In addition, the short-term incubation time did not provide enough opportunity to measure differences in cell proliferation.

The evaluation also noted the immune response to a single stimulus, limiting the analysis of the functional response of immune cells to other stimuli or pathogens.

Implications

Reduced immune response, accelerated pathogen activity, and heightened viral shedding in astronauts in space pose significant risks for both short- and long-term space travel.

Dr. Spatz expresses concern about the growing public demand for space travel, as well:

“Early in the space program, most astronauts were young and extremely healthy, but now they tend to have much more training and are older. In addition, […] with the commercialization of spaceflight, there will be many older and less healthy individuals experiencing microgravity.”

The lead and senior study authors believe that their team’s work can aid in developing interventions to reduce the consequences of suppressed immunity during spaceflight.

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