title: Spaceflight and simulated microgravity cause a significant reduction of key gene expression in early T-cell activation.
abstract: Healthy immune function depends on precise regulation of lymphocyte activation. During the National Aeronautics and Space Administration (NASA) Apollo and Shuttle eras, multiple spaceflight studies showed depressed lymphocyte activity under microgravity (μg) conditions. Scientists on the ground use two models of simulated μg (sμg): 1) the rotating wall vessel (RWV) and 2) the random positioning machine (RPM), to study the effects of altered gravity on cell function before advancing research to the true μg when spaceflight opportunities become available on the International Space Station (ISS). The objective of this study is to compare the effects of true μg and sμg on the expression of key early T-cell activation genes in mouse splenocytes from spaceflight and ground animals. For the first time, we compared all three conditions of microgravity spaceflight, RPM, and RWV during immune gene activation of Il2, Il2rα, Ifnγ, and Tagap; moreover, we confirm two new early T-cell activation genes, Iigp1 and Slamf1. Gene expression for all samples was analyzed using quantitative real-time PCR (qRT-PCR). Our results demonstrate significantly increased gene expression in activated ground samples with suppression of mouse immune function in spaceflight, RPM, and RWV samples. These findings indicate that sμg models provide an excellent test bed for scientists to develop baseline studies and augment true μg in spaceflight experiments. Ultimately, sμg and spaceflight studies in lymphocytes may provide insight into novel regulatory pathways, benefiting both future astronauts and those here on earth suffering from immune disorders.
authors.affiliation: Hughes-Fulford Laboratory, Department of Medicine Metabolism Division San Francisco Department of Veterans Affairs Medical Center and Northern California Institute for Research and Education, San Francisco, California; and.
authors.forename: Emily M
authors.initials: EM
authors.lastname: Martinez
authors.affiliation: Hughes-Fulford Laboratory, Department of Medicine Metabolism Division San Francisco Department of Veterans Affairs Medical Center and Northern California Institute for Research and Education, San Francisco, California; and.
authors.forename: Miya C
authors.initials: MC
authors.lastname: Yoshida
authors.affiliation: Hughes-Fulford Laboratory, Department of Medicine Metabolism Division San Francisco Department of Veterans Affairs Medical Center and Northern California Institute for Research and Education, San Francisco, California; and.
authors.forename: Tara Lynne T
authors.initials: TL
authors.lastname: Candelario
authors.affiliation: Hughes-Fulford Laboratory, Department of Medicine Metabolism Division San Francisco Department of Veterans Affairs Medical Center and Northern California Institute for Research and Education, San Francisco, California; and Department of Medicine, University of California, San Francisco, California m.hughes-fulford@ucsf.edu milliehf@gmail.com.
authors.forename: Millie
authors.initials: M
authors.lastname: Hughes-Fulford
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D015536:Down-Regulation; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism; D007108:Immune Tolerance / Q000235:genetics*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics*; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013026:Space Flight; D013154:Spleen / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018474:Weightlessness Simulation
chemical_list: D020690:GTPase-Activating Proteins; C508018:Il2ra protein, mouse; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D012333:RNA, Messenger; D007371:Interferon-gamma
keywords: T-cell activation; immunosuppression; spaceflight and microgravity