Scientific Reports (Jun 2021)

Human immune system adaptations to simulated microgravity revealed by single-cell mass cytometry

  • J. M. Spatz,
  • M. Hughes Fulford,
  • A. Tsai,
  • D. Gaudilliere,
  • J. Hedou,
  • E. Ganio,
  • M. Angst,
  • N. Aghaeepour,
  • Brice Gaudilliere

DOI
https://doi.org/10.1038/s41598-021-90458-2
Journal volume & issue
Vol. 11, no. 1
pp. 1 – 10

Abstract

Read online

Abstract Exposure to microgravity (µG) during space flights produces a state of immunosuppression, leading to increased viral shedding, which could interfere with long term missions. However, the cellular mechanisms that underlie the immunosuppressive effects of µG are ill-defined. A deep understanding of human immune adaptations to µG is a necessary first step to design data-driven interventions aimed at preserving astronauts’ immune defense during short- and long-term spaceflights. We employed a high-dimensional mass cytometry approach to characterize over 250 cell-specific functional responses in 18 innate and adaptive immune cell subsets exposed to 1G or simulated (s)µG using the Rotating Wall Vessel. A statistically stringent elastic net method produced a multivariate model that accurately stratified immune responses observed in 1G and sµG (p value 2E−4, cross-validation). Aspects of our analysis resonated with prior knowledge of human immune adaptations to µG, including the dampening of Natural Killer, CD4+ and CD8+ T cell responses. Remarkably, we found that sµG enhanced STAT5 signaling responses of immunosuppressive Tregs. Our results suggest µG exerts a dual effect on the human immune system, simultaneously dampening cytotoxic responses while enhancing Treg function. Our study provides a single-cell readout of sµG-induced immune dysfunctions and an analytical framework for future studies of human immune adaptations to human long-term spaceflights.