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- Title
Single-cell analysis identifies conserved features of immune dysfunction in simulated microgravity and spaceflight.
- Authors
Wu, Fei; Du, Huixun; Overbey, Eliah; Kim, JangKeun; Makhijani, Priya; Martin, Nicolas; Lerner, Chad A.; Nguyen, Khiem; Baechle, Jordan; Valentino, Taylor R.; Fuentealba, Matias; Bartleson, Juliet M.; Halaweh, Heather; Winer, Shawn; Meydan, Cem; Garrett-Bakelman, Francine; Sayed, Nazish; Melov, Simon; Muratani, Masafumi; Gerencser, Akos A.
- Abstract
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. The phenotype and function of immune cells could change during spaceflight. Here the authors use simulated microgravity, coupled to validation with spaceflight data, to assess whether there are distinct gene expression changes in resting and TLR 7/8 stimulated PBMCs and found conserved changes in IFN signalling, the cytoskeleton, IL-6 and sirtuin signalling.
- Subjects
MONONUCLEAR leukocytes; REDUCED gravity environments; SPACE flight; TOLL-like receptors; INTERFERON receptors; KILLER cells
- Publication
Nature Communications, 2024, Vol 15, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-42013-y