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

Abstract

During spaceflights, astronauts face different forms of stress (e.g., socio-environmental and gravity stresses) that impact physiological functions and particularly the immune system. In this context, little is known about the effect of such stress on dendritic cells (DCs). First, we showed that hypergravity, but not chronic ultra-mild stress, a socio-environmental stress, induced a less mature phenotype characterized by a decreased expression of MHCII and co-stimulatory molecules. Next, using the random positioning machine (RPM), we studied the direct effects of simulated microgravity on either splenic DCs or Flt-3L-differentiated bone marrow dendritic cells (BMDCs). Simulated microgravity was found to reduce the BM-conventional DC (cDC) and splenic cDC activation/maturation phenotype. Consistent with this, BMDCs displayed a decreased production of pro-inflammatory cytokines when exposed to microgravity compared to the normogravity condition. The induction of a more immature phenotype in microgravity than in control DCs correlated with an alteration of the NFκB signaling pathway. Since the DC phenotype is closely linked to their function, we studied the effects of microgravity on DCs and found that microgravity impaired their ability to induce naïve CD4 T cell survival, proliferation, and polarization. Thus, a deregulation of DC function is likely to induce immune deregulation, which could explain the reduced efficiency of astronauts’ immune response.

Current Knowledge about the Impact of Microgravity on Gene Regulation

“…The authors demonstrated that non-matured RPM-exposed BMDCs exhibited a more immature phenotype, compared to the control BMDCs. These data correlated with an impaired ability of BMDCs to express pro-inflammatory cytokine transcripts as shown in Figure 3A of [ 130 ]. A deregulation of DC function is likely responsible for inducing immune deregulation during spaceflight [ 130 ].…”

“…These data correlated with an impaired ability of BMDCs to express pro-inflammatory cytokine transcripts as shown in Figure 3A of [ 130 ]. A deregulation of DC function is likely responsible for inducing immune deregulation during spaceflight [ 130 ].…”

“…Space travelers face different forms of stress influencing their immune system. A paper published in January 2023 showed that RPM exposure altered the Nuclear Factor κB signaling pathway and affects murine dendritic cells (DC) and their function [ 130 ]. Splenic DC or Flt-3L-differentiated bone marrow DC (BMDCs) were exposed to the RPM.…”

“…Splenic DC or Flt-3L-differentiated bone marrow DC (BMDCs) were exposed to the RPM. S-µ g reduced BM-conventional DC (cDC) as well as splenic cDC activation/maturation phenotype changes [ 130 ]. BMDCs exhibited a decreased production of pro-inflammatory cytokines when exposed to the RPM.…”