Simulated Microgravity Disrupts Nuclear Factor κB Signaling and Impairs Murine Dendritic Cell Phenotype and Function

Area of Science:

• Spaceflight immunology
• Cellular immunology
• Dendritic cell biology

Background:

• Astronauts experience physiological stress during spaceflight, impacting immune function.
• The effects of spaceflight stress on dendritic cells (DCs), crucial immune regulators, remain largely unknown.

Purpose of the Study:

• To investigate the impact of simulated microgravity and hypergravity on dendritic cell (DC) phenotype, activation, and function.
• To elucidate the underlying molecular mechanisms, including NFκB signaling pathway alterations.

Main Methods:

• Utilized the random positioning machine (RPM) to simulate microgravity.
• Examined dendritic cells (DCs) from spleen and bone marrow (BMDCs) under simulated microgravity and normogravity conditions.
• Assessed DC maturation markers (MHCII, co-stimulatory molecules), cytokine production, NFκB pathway activation, and T cell interactions.

Main Results:

• Simulated microgravity reduced DC activation and maturation, characterized by decreased MHCII and co-stimulatory molecule expression.
• Microgravity exposure led to reduced pro-inflammatory cytokine production by BMDCs.
• Microgravity impaired DC function in supporting naïve CD4 T cell survival, proliferation, and polarization.
• Hypergravity, but not chronic ultra-mild stress, also induced a less mature DC phenotype.

Conclusions:

• Simulated microgravity induces an immature DC phenotype and alters NFκB signaling, leading to impaired DC function.
• Dysregulated DC function during spaceflight may contribute to the observed immune deregulation in astronauts.
• These findings highlight the critical need to address immune system changes in space exploration.