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

Autor: Wu F; Buck Institute for Research on Aging, Novato, CA, 94945, USA., Du H; Buck Institute for Research on Aging, Novato, CA, 94945, USA.; Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, 90089, USA., Overbey E; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, 10021, USA., Kim J; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, 10021, USA., Makhijani P; Buck Institute for Research on Aging, Novato, CA, 94945, USA.; Department of Immunology, University of Toronto, Toronto, ON, M5S 1A8, Canada., Martin N; Buck Institute for Research on Aging, Novato, CA, 94945, USA., Lerner CA; Buck Institute for Research on Aging, Novato, CA, 94945, USA., Nguyen K; Buck Institute for Research on Aging, Novato, CA, 94945, USA., Baechle J; Buck Institute for Research on Aging, Novato, CA, 94945, USA., Valentino TR; Buck Institute for Research on Aging, Novato, CA, 94945, USA., Fuentealba M; Buck Institute for Research on Aging, Novato, CA, 94945, USA., Bartleson JM; Buck Institute for Research on Aging, Novato, CA, 94945, USA., Halaweh H; Buck Institute for Research on Aging, Novato, CA, 94945, USA., Winer S; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, M5S 1A8, Canada.; Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada., Meydan C; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, 10021, USA., Garrett-Bakelman F; Department of Medicine, University of Virginia, Charlottesville, VA, USA.; Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA, USA., Sayed N; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, 94305, USA., Melov S; Buck Institute for Research on Aging, Novato, CA, 94945, USA., Muratani M; Transborder Medical Research Center, University of Tsukuba, Ibaraki, 305-8575, Japan.; Department of Genome Biology, Faculty of Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan., Gerencser AA; Buck Institute for Research on Aging, Novato, CA, 94945, USA., Kasler HG; Buck Institute for Research on Aging, Novato, CA, 94945, USA., Beheshti A; Blue Marble Space Institute of Science, Space Biosciences Division, NASA Ames Research Center, Moffett Field, CA, 94043, USA.; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA., Mason CE; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, 10021, USA. chm2042@med.cornell.edu.; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, 10021, USA. chm2042@med.cornell.edu.; WorldQuant Initiative for Quantitative Prediction, Weill Cornell Medicine, New York, NY, 10021, USA. chm2042@med.cornell.edu.; The Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, 10021, USA. chm2042@med.cornell.edu., Furman D; Buck Institute for Research on Aging, Novato, CA, 94945, USA. DFurman@buckinstitute.org.; Stanford 1000 Immunomes Project, Stanford University School of Medicine, Stanford, CA, USA. DFurman@buckinstitute.org.; Institute for Research in Translational Medicine, Universidad Austral, CONICET, Pilar, Buenos Aires, Argentina. DFurman@buckinstitute.org., Winer DA; Buck Institute for Research on Aging, Novato, CA, 94945, USA. dwiner@buckinstitute.org.; Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, 90089, USA. dwiner@buckinstitute.org.; Department of Immunology, University of Toronto, Toronto, ON, M5S 1A8, Canada. dwiner@buckinstitute.org.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, M5S 1A8, Canada. dwiner@buckinstitute.org.; Division of Cellular & Molecular Biology, Toronto General Hospital Research Institute (TGHRI), University Health Network, Toronto, ON, M5G 1L7, Canada. dwiner@buckinstitute.org.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Jun 11; Vol. 15 (1), pp. 4795. Date of Electronic Publication: 2024 Jun 11.
DOI: 10.1038/s41467-023-42013-y
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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