As humanity prepares for a new era of lunar exploration and future missions to Mars, scientists are studying a critical question: How will reduced gravity affect the human immune system?
Astronauts will not experience Earth’s normal gravity on the Moon or Mars. The Moon has only about 16% of Earth’s gravity (0.16 g), while Mars has about 38% (0.38 g). Although these environments are not completely weightless, researchers are finding that even partial gravity can change how immune cells interact with blood vessels.
A new study led by Yu Du and colleagues investigated how immune cells behave under lunar and Martian gravity. The researchers discovered changes in immune-cell movement, attachment to blood-vessel cells, adhesion molecules and the internal structure of endothelial cells—the cells that line our blood vessels.
The findings suggest that partial gravity could influence the body’s ability to control inflammation and move immune cells through blood vessels.
Why Immune Health Matters in Space
Spaceflight is already known to affect the human immune system. Research from previous space missions has shown that astronauts can experience changes in immune-cell activity, potentially increasing vulnerability to infections and other health problems.
Microgravity—the near-weightless environment experienced aboard spacecraft—has received considerable scientific attention. Studies have found changes in the behavior of monocytes, T cells and other immune cells under microgravity conditions.
However, future astronauts traveling to the Moon and Mars will spend much of their time in partial gravity rather than complete weightlessness.
That raises an important question: Does partial gravity cause the same biological changes as microgravity?
The new research provides some early clues.
The Moon and Mars Create Very Different Gravity Environments
Earth's gravity is defined as 1 g. On the Moon, gravity is approximately 0.16 g, while Mars has approximately 0.38 g.
These differences may seem relatively small compared with the complete absence of gravity in orbit, but cells are extremely sensitive to mechanical forces.
The researchers wanted to see whether lunar and Martian gravity could change how immune cells interact with the walls of blood vessels.
To investigate this, they used THP-1 cells, a laboratory model of human monocytes, together with HUVECs, human endothelial cells that form a model of the inner lining of blood vessels.
The cells were placed inside a specially designed flow chamber and exposed to lunar and Martian gravity during parabolic flight experiments.
Parabolic aircraft flights can briefly reproduce different gravity levels. In this experiment, the lunar-gravity phase lasted about 24 seconds, while the Martian-gravity phase lasted approximately 33 seconds.
Although these periods are extremely short, they allow scientists to directly study how cells respond to unusual gravitational forces.
Immune Cells Moved Faster in Partial Gravity
One of the clearest observations involved the movement of THP-1 immune cells through the flow chamber.
Under lunar and Martian gravity, the cells showed an increased floating speed compared with normal Earth gravity.
The researchers suggest that weaker gravity changes the forces acting on suspended cells, causing them to become more centralized within the flowing liquid.
This matters because immune cells normally need to interact with blood-vessel walls before they can leave the bloodstream and enter surrounding tissues.
Normally, immune cells slow down, attach to the vessel wall, crawl along its surface and eventually move through the endothelial layer.
If their movement and contact with the vessel wall change, the entire immune-cell recruitment process could be affected.
Lower Gravity Meant Less Cell Attachment
The study also found that THP-1 cells showed progressively lower adhesion to endothelial cells as gravity decreased.
In simple terms, the immune cells became less likely to firmly attach to the blood-vessel-like surface under partial gravity.
This could be important because adhesion is a crucial step in the body's immune response.
When inflammation occurs, immune cells circulating through the bloodstream must identify the affected area, attach to the endothelial surface and eventually pass through the blood-vessel wall.
Changes in this process could potentially influence how efficiently immune cells reach sites of inflammation or infection.
However, the researchers emphasize that these laboratory observations do not yet demonstrate that astronauts will experience impaired immunity in the same way during long-duration lunar or Martian missions.
Key Adhesion Molecules Increased
Interestingly, the reduced cell attachment occurred alongside increased levels of certain adhesion molecules.
The researchers examined Mac-1, found on immune cells, and ICAM-1, found on endothelial cells.
Both molecules are involved in interactions between immune cells and blood-vessel walls.
Their expression increased under lunar and Martian gravity, with the effect becoming stronger when the cells were exposed to tumor necrosis factor (TNF), a molecule associated with inflammation.
This suggests that reduced gravity and an inflammatory environment may interact with each other.
Rather than simply switching the immune system "off," partial gravity appears capable of reorganizing several parts of the cellular machinery involved in inflammation and immune-cell recruitment.
Gravity Also Changed the Structure of Blood-Vessel Cells
The researchers investigated another important feature: the cytoskeleton.
The cytoskeleton is an internal network of protein structures that helps cells maintain their shape and respond to mechanical forces.
One important component is F-actin, which forms filament networks inside cells.
Under partial gravity, the endothelial cells showed reduced intracellular F-actin networks and stronger directional organization. Stress fibers became more aligned toward the cell borders.
TNF-induced inflammation intensified these changes.
This is significant because the cytoskeleton helps regulate how endothelial cells maintain the blood-vessel barrier, respond to mechanical forces and interact with immune cells.
If its organization changes, the behavior of the endothelial layer could change as well.
The Moon May Produce Stronger Effects Than Mars
The researchers observed differences between the two gravity levels.
Overall, the changes appeared to be more pronounced under lunar gravity (0.16 g) than Martian gravity (0.38 g).
This suggests that the biological response may not simply be a matter of "gravity versus no gravity." Instead, cells could respond differently depending on the exact gravitational environment.
The researchers also found evidence suggesting that some effects became clearer when the cells were exposed to an inflammatory condition.
This is particularly interesting because astronauts may encounter multiple stress factors during deep-space missions, including radiation, confinement, altered sleep patterns and physiological stress.
But There Are Important Limitations
The experiment represents an important step, but it does not provide a complete picture of how the human immune system will behave on the Moon or Mars.
The gravity exposure lasted only seconds during each parabolic flight. Humans, by contrast, could spend weeks or months living in partial gravity.
The researchers therefore emphasize the need for longer-duration experiments using simulated lunar and Martian gravity.
Another limitation is that parabolic flights involve brief periods of hypergravity, reaching around 1.8 g, before and after the reduced-gravity phase. Some of the observed cellular changes could therefore include effects associated with these transitions.
The study also used cultured cells rather than a complete human body, meaning the results cannot directly predict infection risk or immune-system performance in astronauts.
A Crucial Step Toward Moon and Mars Missions
Returning humans to the Moon and eventually sending astronauts to Mars will require much more than powerful rockets and advanced spacesuits.
Scientists must understand how the human body responds to environments that have never been experienced for long periods by modern humans.
This study suggests that partial gravity can influence the physical interaction between immune cells and blood-vessel cells, while also changing adhesion molecules and the internal cytoskeleton of endothelial cells.
The findings show similarities to some effects previously observed in microgravity, but they also suggest that the magnitude of these effects may depend on the level of gravity.
Future experiments involving longer exposure to 0.16 g and 0.38 g could reveal whether these short-term cellular changes persist, become stronger or eventually adapt over time.
As humanity prepares for sustained exploration of the Moon and Mars, understanding these microscopic changes could become an important part of protecting astronaut health—and ensuring that the human immune system remains capable of responding effectively millions of kilometers from Earth.
Reference: Du, Y., Han, B., Biere, K. et al. Lunar and Martian gravity alter immune cell interactions with endothelia in parabolic flight. npj Microgravity 11, 4 (2025). https://doi.org/10.1038/s41526-024-00456-7
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