Transcriptomics analysis reveals potential mechanisms underlying mitochondrial dysfunction and T cell exhaustion in astronauts’ blood cells in space
IntroductionThe impact of spaceflight on the immune system and mitochondria has been investigated for decades. However, the molecular mechanisms underlying spaceflight-induced immune dysregulations are still unclear.MethodsIn this study, blood from eleven crewmembers was collected before and during...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1512578/full |
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| author | Maria Moreno-Villanueva Maria Moreno-Villanueva Luis E. Jimenez-Chavez Luis E. Jimenez-Chavez Stephanie Krieger Liang-Hao Ding Ye Zhang Adriana Babiak-Vazquez Mark Berres Sandra Splinter Kristen E. Pauken Brian C. Schaefer Brian E. Crucian Honglu Wu |
| author_facet | Maria Moreno-Villanueva Maria Moreno-Villanueva Luis E. Jimenez-Chavez Luis E. Jimenez-Chavez Stephanie Krieger Liang-Hao Ding Ye Zhang Adriana Babiak-Vazquez Mark Berres Sandra Splinter Kristen E. Pauken Brian C. Schaefer Brian E. Crucian Honglu Wu |
| author_sort | Maria Moreno-Villanueva |
| collection | DOAJ |
| description | IntroductionThe impact of spaceflight on the immune system and mitochondria has been investigated for decades. However, the molecular mechanisms underlying spaceflight-induced immune dysregulations are still unclear.MethodsIn this study, blood from eleven crewmembers was collected before and during International Space Station (ISS) missions. Transcriptomic analysis was performed in isolated peripheral blood mononuclear cells (PBMCs) using RNA-sequencing. Differentially expresses genes (DEG) in space were determined by comparing of the inflight to the preflight samples. Pathways and statistical analyses of these DEG were performed using the Ingenuity Pathway Analysis (IPA) tool.ResultsIn comparison to pre-flight, a total of 2030 genes were differentially expressed in PBMC collected between 135 and 210 days in orbit, which included a significant number of surface receptors. The dysregulated genes and pathways were mostly involved in energy and oxygen metabolism, immune responses, cell adhesion/migration and cell death/survival.DiscussionBased on the DEG and the associated pathways and functions, we propose that mitochondria dysfunction was caused by constant modulation of mechano-sensing receptors in microgravity, which triggered a signaling cascade that led to calcium overloading in mitochondria. The response of PBMC in space shares T-cell exhaustion features, likely initiated by microgravity than by infection. Consequences of mitochondria dysfunction include immune dysregulation and prolonged cell survival which potentially explains the reported findings of inhibition of T cell activation and telomere lengthening in astronauts.ConclusionOur study potentially identifies the upstream cause of mitochondria dysfunction and the downstream consequences in immune cells. |
| format | Article |
| id | doaj-art-15c4eb1451d748d0bafc98099ae67bc4 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-15c4eb1451d748d0bafc98099ae67bc42025-01-20T05:23:39ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.15125781512578Transcriptomics analysis reveals potential mechanisms underlying mitochondrial dysfunction and T cell exhaustion in astronauts’ blood cells in spaceMaria Moreno-Villanueva0Maria Moreno-Villanueva1Luis E. Jimenez-Chavez2Luis E. Jimenez-Chavez3Stephanie Krieger4Liang-Hao Ding5Ye Zhang6Adriana Babiak-Vazquez7Mark Berres8Sandra Splinter9Kristen E. Pauken10Brian C. Schaefer11Brian E. Crucian12Honglu Wu13National Aeronautics and Space Administration, Johnson Space Center, Houston, TX, United StatesDepartment of Sport Science, University of Konstanz, Konstanz, GermanyNational Aeronautics and Space Administration, Johnson Space Center, Houston, TX, United StatesCollege of Medicine, University of Central Florida, Orlando, FL, United StatesKBR, Houston, TX, United StatesDepartment of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, United StatesNational Aeronautics and Space Administration, Kennedy Space Center, Cape Canaveral, FL, United StatesDepartment of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, United StatesBioinformatics Resource and Gene Expression Center, University of Wisconsin, Madison, WI, United StatesBioinformatics Resource and Gene Expression Center, University of Wisconsin, Madison, WI, United StatesDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, United StatesNational Aeronautics and Space Administration, Johnson Space Center, Houston, TX, United StatesNational Aeronautics and Space Administration, Johnson Space Center, Houston, TX, United StatesIntroductionThe impact of spaceflight on the immune system and mitochondria has been investigated for decades. However, the molecular mechanisms underlying spaceflight-induced immune dysregulations are still unclear.MethodsIn this study, blood from eleven crewmembers was collected before and during International Space Station (ISS) missions. Transcriptomic analysis was performed in isolated peripheral blood mononuclear cells (PBMCs) using RNA-sequencing. Differentially expresses genes (DEG) in space were determined by comparing of the inflight to the preflight samples. Pathways and statistical analyses of these DEG were performed using the Ingenuity Pathway Analysis (IPA) tool.ResultsIn comparison to pre-flight, a total of 2030 genes were differentially expressed in PBMC collected between 135 and 210 days in orbit, which included a significant number of surface receptors. The dysregulated genes and pathways were mostly involved in energy and oxygen metabolism, immune responses, cell adhesion/migration and cell death/survival.DiscussionBased on the DEG and the associated pathways and functions, we propose that mitochondria dysfunction was caused by constant modulation of mechano-sensing receptors in microgravity, which triggered a signaling cascade that led to calcium overloading in mitochondria. The response of PBMC in space shares T-cell exhaustion features, likely initiated by microgravity than by infection. Consequences of mitochondria dysfunction include immune dysregulation and prolonged cell survival which potentially explains the reported findings of inhibition of T cell activation and telomere lengthening in astronauts.ConclusionOur study potentially identifies the upstream cause of mitochondria dysfunction and the downstream consequences in immune cells.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1512578/fullspaceflighttranscriptomicsastronauts’ healthmitochondriaimmune dysfunctiontelomere lengthening |
| spellingShingle | Maria Moreno-Villanueva Maria Moreno-Villanueva Luis E. Jimenez-Chavez Luis E. Jimenez-Chavez Stephanie Krieger Liang-Hao Ding Ye Zhang Adriana Babiak-Vazquez Mark Berres Sandra Splinter Kristen E. Pauken Brian C. Schaefer Brian E. Crucian Honglu Wu Transcriptomics analysis reveals potential mechanisms underlying mitochondrial dysfunction and T cell exhaustion in astronauts’ blood cells in space Frontiers in Immunology spaceflight transcriptomics astronauts’ health mitochondria immune dysfunction telomere lengthening |
| title | Transcriptomics analysis reveals potential mechanisms underlying mitochondrial dysfunction and T cell exhaustion in astronauts’ blood cells in space |
| title_full | Transcriptomics analysis reveals potential mechanisms underlying mitochondrial dysfunction and T cell exhaustion in astronauts’ blood cells in space |
| title_fullStr | Transcriptomics analysis reveals potential mechanisms underlying mitochondrial dysfunction and T cell exhaustion in astronauts’ blood cells in space |
| title_full_unstemmed | Transcriptomics analysis reveals potential mechanisms underlying mitochondrial dysfunction and T cell exhaustion in astronauts’ blood cells in space |
| title_short | Transcriptomics analysis reveals potential mechanisms underlying mitochondrial dysfunction and T cell exhaustion in astronauts’ blood cells in space |
| title_sort | transcriptomics analysis reveals potential mechanisms underlying mitochondrial dysfunction and t cell exhaustion in astronauts blood cells in space |
| topic | spaceflight transcriptomics astronauts’ health mitochondria immune dysfunction telomere lengthening |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1512578/full |
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