Immune potency of bioreactor-aged dendritic cells in 3D collagen matrices

Abstract

Abstract The processes of aging and space travel both have significant adverse effects on the immune system, resulting in increased susceptibility to infections. Using simulated microgravity platforms, such as the random positioning machine (RPM), on Earth allows us to investigate these effects to better facilitate future space travel and our understanding of the aging immune system. Dendritic cells (DCs) are key players in linking the innate and adaptive immune responses. Their distinct differentiation and maturation phases play vital roles in presenting antigens and mounting effective T-cell responses. However, DCs primarily reside in tissues such as the skin and lymph nodes. To date, no studies have effectively investigated the effects of aging via RPM on DCs in their native microenvironment. With 3D biomimetic collagen hydrogels, we can study the effects on DCs in more physiologically relevant microenvironments. In this study, we investigated the effects of loose and dense culture matrices on the phenotype, function, and transcriptome profile of immature and mature DCs utilizing an RPM to simulate an accelerated aging model. Our data indicate that an aged, or loose tissue microenvironment, and exposure to RPM conditions decrease the immunogenicity of iDCs and mDCs. Interestingly, cells cultured in dense matrices experienced fewer effects by the RPM at the transcriptome level.