Single-cell analysis identifies conserved features of immune dysfunction in simulated microgravity and spaceflight.

Area of Science:

• Space biology and immunology
• Single-cell transcriptomics
• Immunological dysfunction

Background:

• Microgravity is known to cause immunological dysfunction, but the underlying mechanisms remain unclear.
• Understanding these changes is crucial for astronaut health during long-duration space missions.

Purpose of the Study:

• To characterize gene and pathway alterations in human peripheral blood mononuclear cells (PBMCs) under simulated microgravity.
• To identify potential countermeasures for microgravity-induced immune alterations.

Main Methods:

• Single-cell RNA sequencing and super-resolution microscopy of PBMCs exposed to simulated microgravity.
• Analysis of data from space missions (Inspiration-4, JAXA) and mouse models on the ISS.
• Machine learning to identify compounds affecting microgravity-associated immune cell transcription.

Main Results:

• Microgravity alters pathways including cytoskeleton, interferon signaling, pyroptosis, and innate inflammation.
• Monocyte inflammatory parameters are affected, while T cell and NK cell functionality is impaired.
• The flavonol quercetin reversed most abnormal pathways identified through machine learning.

Conclusions:

• Microgravity significantly alters specific immune cell pathways and functions.
• Quercetin demonstrates potential as a countermeasure to mitigate microgravity-induced immune dysregulation.
• These findings provide a basis for developing strategies to maintain immune health during space exploration.