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

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 understand...

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Autores principales:	J. M. Spatz, M. Hughes Fulford, A. Tsai, D. Gaudilliere, J. Hedou, E. Ganio, M. Angst, N. Aghaeepour, Brice Gaudilliere
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/01a56640835b4c7895b0810e8472400d
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spelling	oai:doaj.org-article:01a56640835b4c7895b0810e8472400d2021-12-02T17:30:53ZHuman immune system adaptations to simulated microgravity revealed by single-cell mass cytometry10.1038/s41598-021-90458-22045-2322https://doaj.org/article/01a56640835b4c7895b0810e8472400d2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90458-2https://doaj.org/toc/2045-2322Abstract 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.J. M. SpatzM. Hughes FulfordA. TsaiD. GaudilliereJ. HedouE. GanioM. AngstN. AghaeepourBrice GaudilliereNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q J. M. Spatz M. Hughes Fulford A. Tsai D. Gaudilliere J. Hedou E. Ganio M. Angst N. Aghaeepour Brice Gaudilliere Human immune system adaptations to simulated microgravity revealed by single-cell mass cytometry
description	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.
format	article
author	J. M. Spatz M. Hughes Fulford A. Tsai D. Gaudilliere J. Hedou E. Ganio M. Angst N. Aghaeepour Brice Gaudilliere
author_facet	J. M. Spatz M. Hughes Fulford A. Tsai D. Gaudilliere J. Hedou E. Ganio M. Angst N. Aghaeepour Brice Gaudilliere
author_sort	J. M. Spatz
title	Human immune system adaptations to simulated microgravity revealed by single-cell mass cytometry
title_short	Human immune system adaptations to simulated microgravity revealed by single-cell mass cytometry
title_full	Human immune system adaptations to simulated microgravity revealed by single-cell mass cytometry
title_fullStr	Human immune system adaptations to simulated microgravity revealed by single-cell mass cytometry
title_full_unstemmed	Human immune system adaptations to simulated microgravity revealed by single-cell mass cytometry
title_sort	human immune system adaptations to simulated microgravity revealed by single-cell mass cytometry
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/01a56640835b4c7895b0810e8472400d
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Human immune system adaptations to simulated microgravity revealed by single-cell mass cytometry

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