An investigation by Sweden’s Karolinska Institutet delves into the interplay between microgravity and the immune system. The outcomes, presented in Science Advances, offer a glimpse into the potential reasons behind the diminished vigor and potency of astronauts’ T cells combating infections.

“If astronauts are to be able to undergo safe space missions, we need to understand how their immune systems are affected and try to find ways to counter harmful changes to it,” says study leader Lisa Westerberg, principal researcher at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet.

The researchers couldn’t study the effects of microgravity on astronauts’ immune systems directly in space, so they went an alternate route. They simulated weightlessness on eight healthy participants who were subjected to dry immersion over the span of 21 days.

Unlike traditional immersion in water, dry immersion involves reclining in a special dry immersion facility. This facility resembles a waterbed and allows the body to be partially or completely immersed in a dry medium, such as a bed filled with small particles like grains or sand.

During dry immersion, the body experiences a sensation of weightlessness because it is effectively suspended in the medium. This simulates the physiological changes that occur in space, including the redistribution of bodily fluids, changes in bone density, and alterations in muscle tone.

The researchers analyzed blood samples from the volunteers before the experiment started, at seven, 14 and 21 days after the start, and seven days after the experiment ended. For each sample, they isolated CD3+ T cells and zoomed in on transcriptomes — the collection of all RNA molecules. RNA, or ribonucleic acid, plays a crucial role in the process of gene expression, where genetic information stored in DNA is converted into functional molecules like proteins.

Transcriptomes provide insight into which genes are active and producing RNA in a particular biological sample. By studying transcriptomes in the volunteers who went through the dry immersion, scientists can thus understand how different genes are regulated and respond to weightlessness.

Indeed, the scientists discovered changes in T cell related gene expression due to dry immersion exposure at various time points. The most significant changes occurred two weeks after the dry immersion exposure, with the immune cells becoming less “mature”.

T cells are a crucial component of the immune system responsible for recognizing and eliminating various threats, such as infected cells, cancer cells, and foreign invaders. They play a central role in adaptive immunity, where the immune system tailors its response to specific pathogens. But to become effective “soldiers”, the T cells have to undergo a process of maturation and specialization.

When transcriptomes regulating T cell expression change, several consequences can arise, including a reduced ability to mount effective immune responses against infections and abnormal cells, an increased risk of autoimmune diseases due to the potential for attacking healthy tissues, decreased diversity of T cell receptors limiting the immune system’s adaptability, and more.

The study found that the T cells’ transcriptional profile on day 21 — at peak dry immersion — resembled that seven days before indicating that they had “adapted” to life in space. This looks like good news but seven days after “returning” to Earth’s gravity, T cells once again exhibited a modified transcriptional profile. It’s not clear yet how concerning this is.

“The T cells began to resemble more so-called naïve T cells, which have not yet encountered any intruders,” said Carlos Gallardo Dodd, Ph.D. student at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet. “This could mean that they take longer to be activated and thus become less effective at fighting tumor cells and infections.”

These results could have a significant bearing on the security of future human spaceflight. Damage to the immune system, which protects the body from infections and diseases, could negatively affect astronauts in space. However, researchers can devise therapies that protect the immune system during long-duration spaceflight if they learn how it reacts to microgravity.

There are, however, important caveats to this study that must be acknowledged. Only eight participants were used, and only T-cell transcriptomes were analyzed. To get a full picture of the immune response in space, more research needs to be done to see how microgravity affects other immune cells and systems.

Despite these caveats, the study’s results greatly advance our understanding of how the human body reacts in microgravity. The study implies that although microgravity significantly alters the immune system, it can also adapt to these new environmental conditions. Recovery from microgravity’s effects on the immune system is encouraging news for the future of human spaceflight.

This study adds to the growing body of inquiry into the immune system’s reaction to microgravity by posing intriguing new questions about the mechanisms at play. Several genes were differentially expressed in T cells during the dry immersion exposure, but their precise functions remain unknown. The potential for targeting these genes to protect the immune system during spaceflight requires further investigation, as does their role in the immune response to microgravity.

“Our results can pave the way for new treatments that reverse these changes to the immune cells’ genetic program,” Gallardo Dodd said.