Single-cell analysis identifies conserved features of immune dysfunction in simulated microgravity and spaceflight.

Single-Cell Analysis Space Flight Humans Animals Mice Leukocytes, Mononuclear / immunology Weightlessness Simulation Quercetin / pharmacology Signal Transduction Killer Cells, Natural / immunology Weightlessness T-Lymphocytes / immunology Mice, Inbred C57BL Machine Learning Male Female Inflammation / immunology Immunity, Innate

Journal

Nature communications

ISSN: 2041-1723

Titre abrégé: Nat Commun

Pays: England

ID NLM: 101528555

Informations de publication

Date de publication:
11 Jun 2024

Historique:

received: 06 12 2022

accepted: 27 09 2023

medline: 12 6 2024

pubmed: 12 6 2024

entrez: 11 6 2024

Statut: epublish

Résumé

Microgravity is associated with immunological dysfunction, though the mechanisms are poorly understood. Here, using single-cell analysis of human peripheral blood mononuclear cells (PBMCs) exposed to short term (25 hours) simulated microgravity, we characterize altered genes and pathways at basal and stimulated states with a Toll-like Receptor-7/8 agonist. We validate single-cell analysis by RNA sequencing and super-resolution microscopy, and against data from the Inspiration-4 (I4) mission, JAXA (Cell-Free Epigenome) mission, Twins study, and spleens from mice on the International Space Station. Overall, microgravity alters specific pathways for optimal immunity, including the cytoskeleton, interferon signaling, pyroptosis, temperature-shock, innate inflammation (e.g., Coronavirus pathogenesis pathway and IL-6 signaling), nuclear receptors, and sirtuin signaling. Microgravity directs monocyte inflammatory parameters, and impairs T cell and NK cell functionality. Using machine learning, we identify numerous compounds linking microgravity to immune cell transcription, and demonstrate that the flavonol, quercetin, can reverse most abnormal pathways. These results define immune cell alterations in microgravity, and provide opportunities for countermeasures to maintain normal immunity in space.

Identifiants

DOI: 10.1038/s41467-023-42013-y PMID: 38862487

pubmed: 38862487

doi: 10.1038/s41467-023-42013-y

pii: 10.1038/s41467-023-42013-y

doi:

Substances chimiques

Quercetin 9IKM0I5T1E

Types de publication

Journal Article Twin Study

Langues

eng

Sous-ensembles de citation

Pagination

4795

Informations de copyright

Références

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