Prolonged exposure to simulated microgravity diminishes dendritic cell immunogenicity

Nichole Tackett,Stefanie H Baker,Randal K Gregg,Emily K Moore,Jillian H Bradley,Jennifer P Arnold,Stephanie L Minter,Brian Digiacinto

doi:10.1038/s41598-019-50311-z

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.

Highlights

Since the beginning of space exploration, it has been clear that spaceflight promotes changes in the balance between the immune system and the resident microbial population of the human body
Since Phosphorylation of STAT-5 (pSTAT-5) can promote noncanonical activation of NF-κB to promote the immunogenicity of dendritic cells (DC), pSTAT-5 was assessed for differential expression between Static and simulated microgravity (SMG) JAWS II DC
The dendritic cell signaling pathway most impacted by SMG was ERK1/2 with an mean fluorescence intensity (MFI) more than three times that of Static DC (Fig. 1a,b)

Summary

Introduction

Since the beginning of space exploration, it has been clear that spaceflight promotes changes in the balance between the immune system and the resident microbial population of the human body. Using a murine dendritic cell line, JAWS II18, and bone marrow-derived DC (BMDC), we tested the effects of short-term (72 h) and long-term (up to 14 d) exposure to SMG upon dendritic cell maturation and capacity to activate peptide-specific CD4+ OT-II T cell hybridomas (TCH)[19] and CD8+ OT-I T cells. Cell surface proteins, such as MHC II, CD80 and CD86, served as markers of maturation. Our data indicated that short-term SMG culture of DC resulted in an increase in maturation status and T cell reactivity, long-term SMG culture diminished dendritic cell functions

Methods

Results

Conclusion