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Simulated Weightlessness Alters T Cell Gene Expression

NEW YORK – Human T cells rewire their gene expression in response to simulated weightlessness, a new study has found.

Researchers said these findings could help develop treatments for astronauts who often experience immunodeficiency and are more prone to infections after they return from space flights.

In a study published in Science Advances on Friday, researchers from Karolinska Institutet in Sweden exposed eight healthy volunteers to weightless conditions and mapped the transcriptomic changes for three weeks using qPCR gene expression profiling.

While the authors said it is ideal to study the effects of space in the space environment, doing so is fraught with challenges. As such, the researchers turned to a method called dry immersion (DI) to stimulate weightlessness.

For this, they used a custom-made waterbed that stimulates microgravity and tricks the body into thinking it is in a weightless state. During the experiment, the participants were submerged neck down into a thermo-neutral water bath.

"The volunteers sense most of the physiological effects of space flight, such as mechanical and axial unloading and physical inactivity. They have back pain, they increase in length, and have body fluid shift," corresponding author Lisa Westerberg, a researcher in the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet, said in an email.

Next, her team documented the transcriptional changes in T cells from blood samples taken from these volunteers on days seven, 14, and 21 during DI and a week after the exposure.

The findings showed that on day 14, the T cells underwent the most dramatic changes and began to resemble naïve T cells. While the genes related to activation and effector function of T cells were downregulated, genes that define naïve T cells were upregulated, the authors noted.

On day 21, T cells showed signs of adaptation with a transcriptional profile most similar to pre-DI T cells. However, some transcriptional changes persisted in T cells seven days after recovery from the DI. "The study provides new insight into the long-term effects of microgravity by identifying alterations in important T cell gene expression programs," the authors concluded.

It is already well known that space flights impair the human immune system, with these changes persisting long after astronauts return to Earth. In fact, half of the Apollo crew members reported bacterial or viral infection upon returning to Earth, suggesting immune suppression.

As more space flights are planned, studying the changes in the immune system in space is essential to ensure the safety of the astronauts, the authors said.

As a next step, Westerberg said her team wants to use the Esrange Space Centre's sounding rocket platform in Kiruna, Sweden, to study how T cells behave in weightless conditions and how their function is affected.

Westerberg noted that in the current study, limited blood sample sizes did not allow her team could to perform validation experiments, called orthogonal assays, to examine how gene expression changes would translate into changes in the encoded protein and functional properties of T cells.