3D microenvironment attenuates simulated microgravity-mediated changes in T cell transcriptome

Abstract Human space travel and exploration are of interest to both the industrial and scientific community. However, there are many adverse effects of spaceflight on human physiology. In particular, there is a lack of understanding to the extent by which microgravity affects the immune system. T cells, key players of the adaptive immune system and long term immunity, are present not only in blood circulation, but also reside within tissue. As of yet, studies investigating the effects of microgravity on T cells are limited to peripheral blood or traditional 2D cell culture that recapitulates circulating blood. To better mimic interstitial tissue, 3D cell culture has been well established for physiologically and pathologically relevant models. In this work, we utilize 2D and 3D cell culture to gain an understanding of how simulated microgravity affects both circulating and tissue resident T cells. T cells were studied in both resting and activated stages. We found that 3D cell culture attenuates the effects of simulated microgravity on the T cells transcriptome and nuclear irregularities compared to 2D cell culture. Interestingly, simulated microgravity appears to have less effect on activated T cells compared to those in the resting stage. Overall, our work provides novel insights into the effects of simulated microgravity on circulating and tissue resident T cells which could provide benefits for the health of space travelers.