Prolonged exposure to simulated microgravity diminishes dendritic cell immunogenicity

Abstract

Immune dysfunction due to microgravity remains a hurdle in the next step of human space exploration. Dendritic cells (DC) represent a critical component of immunity, given their role in the detection of invaders and the subsequent task of activating T cells to respond and eliminate the threat. Upon encounter with microbes, DC undergo a process of maturation, whereby the cells upregulate the expression of surface proteins and secrete cytokines, both required for the optimal activation of CD4+ and CD8+ T cells. In this study, DC were cultured from 2–14 days in a rotary cell culture system, which generates a simulated microgravity (SMG) environment, and then the cells were assessed for maturation status and the capacity to activate T cells. Short-term culture (<72 h) of DC in SMG resulted in an increased expression of surface proteins associated with maturation and interleukin-6 production. Subsequently, the SMG exposed DC were superior to Static control DC at activating both CD4+ and CD8+ T cells as measured by interleukin-2 and interferon-γ production, respectively. However, long-term culture (4–14 d) of DC in SMG reduced the expression of maturation markers and the capacity to activate T cells as compared to Static DC controls.

Exosomes derived from umbilical cord mesenchymal stem cells in mechanical environment show improved osteochondral activity via upregulation of LncRNA H19

“…Another important aspect of RCCS is the rotational speed. Previous studies have reported speeds ranging from 12 to 48 rpm/min, and no universal rotational speed has been identified [ [26] , [27] , [28] ]. Difference in rotational speed may lead to different mechanical stimulation, which can generate diverse cell states.…”

Simulated microgravity suppresses MAPK pathway‐mediated innate immune response to bacterial infection and induces gut microbiota dysbiosis

“…Since the earliest flights into space in the 1960s, there has been a growing concern about the deleterious effects of exposure to spaceflight environment on human health, among which the immune dysfunction caused by microgravity was clearly defined 1‐8 . Decades ago, nearly half of the astronauts of the Apollo mission acquired infections either during or following their spaceflight, 9 and such an infection has been suggested to manifest only when the immunity is compromised.…”

Putative Receptors for Gravity Sensing in Mammalian Cells: The Effects of Microgravity

“…More recently, microgravity has been shown to reduce the number, differentiation, and polarization of macrophages by affecting the Rat Sarcoma (RAS)/Extracellular signal-regulated kinase (ERK)/Nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) pathway [6]. Moreover, the dendritc maturation and activation of T-cell is also reduced after prolonged microgravity exposure [7]. On the other hand, microgravity increased the resistance of T-cells to dendritic cell activation [8].…”