title: Hypergravity Provokes a Temporary Reduction in CD4+CD8+ Thymocyte Number and a Persistent Decrease in Medullary Thymic Epithelial Cell Frequency in Mice.
abstract: Gravity change affects many immunological systems. We investigated the effects of hypergravity (2G) on murine thymic cells. Exposure of mice to 2G for three days reduced the frequency of CD4+CD8+ thymocytes (DP) and mature medullary thymic epithelial cells (mTECs), accompanied by an increment of keratin-5 and keratin-8 double-positive (K5+K8+) TECs that reportedly contain TEC progenitors. Whereas the reduction of DP was recovered by a 14-day exposure to 2G, the reduction of mature mTECs and the increment of K5+K8+ TEC persisted. Interestingly, a surgical lesion of the inner ear's vestibular apparatus inhibited these hypergravity effects. Quantitative PCR analysis revealed that the gene expression of Aire and RANK that are critical for mTEC function and development were up-regulated by the 3-day exposure and subsequently down-regulated by the 14-day exposure to 2G. Unexpectedly, this dynamic change in mTEC gene expression was independent of the vestibular apparatus. Overall, data suggest that 2G causes a temporary reduction of DP and a persistent reduction of mature mTECs in a vestibular system-dependent manner, and also dysregulates mTEC gene expression without involving the vestibular system. These data might provide insight on the impact of gravity change on thymic functions during spaceflight and living.
authors.affiliation: Division of Cellular and Molecular Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Mouse epigenetics project, ISS/Kibo experiment, Japan Aerospace Exploration Agency, JAXA, Tsukuba, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Tateishi
authors.affiliation: Division of Cellular and Molecular Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Mouse epigenetics project, ISS/Kibo experiment, Japan Aerospace Exploration Agency, JAXA, Tsukuba, Japan.
authors.forename: Nobuko
authors.initials: N
authors.lastname: Akiyama
authors.affiliation: Division of Cellular and Molecular Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Mouse epigenetics project, ISS/Kibo experiment, Japan Aerospace Exploration Agency, JAXA, Tsukuba, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Miyauchi
authors.affiliation: Division of Cellular and Molecular Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Mouse epigenetics project, ISS/Kibo experiment, Japan Aerospace Exploration Agency, JAXA, Tsukuba, Japan.
authors.forename: Riko
authors.initials: R
authors.lastname: Yoshinaga
authors.affiliation: Mouse epigenetics project, ISS/Kibo experiment, Japan Aerospace Exploration Agency, JAXA, Tsukuba, Japan; Laboratory of Developmental Genetics, Center for Experimental Medicine and Systems Biology, The University of Tokyo, Tokyo, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sasanuma
authors.affiliation: Mouse epigenetics project, ISS/Kibo experiment, Japan Aerospace Exploration Agency, JAXA, Tsukuba, Japan; Laboratory Animal Resource Center, University of Tsukuba, Tsukuba, Ibaraki, Japan; Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kudo
authors.affiliation: Mouse epigenetics project, ISS/Kibo experiment, Japan Aerospace Exploration Agency, JAXA, Tsukuba, Japan; Laboratory Animal Resource Center, University of Tsukuba, Tsukuba, Ibaraki, Japan; Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Shimbo
authors.affiliation: Mouse epigenetics project, ISS/Kibo experiment, Japan Aerospace Exploration Agency, JAXA, Tsukuba, Japan; Department of Systems BioMedicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; JST, PRESTO, Kawaguchi, Saitama, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Shinohara
authors.affiliation: Mouse epigenetics project, ISS/Kibo experiment, Japan Aerospace Exploration Agency, JAXA, Tsukuba, Japan; Department of Physiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Obata
authors.affiliation: Division of Cellular and Molecular Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Jun-Ichiro
authors.initials: J
authors.lastname: Inoue
authors.affiliation: Mouse epigenetics project, ISS/Kibo experiment, Japan Aerospace Exploration Agency, JAXA, Tsukuba, Japan; JEM Utilization Center, Human Spaceflight Technology Directorate, JAXA, Tsukuba, Ibaraki, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Shirakawa
authors.affiliation: Mouse epigenetics project, ISS/Kibo experiment, Japan Aerospace Exploration Agency, JAXA, Tsukuba, Japan; JEM Utilization Center, Human Spaceflight Technology Directorate, JAXA, Tsukuba, Ibaraki, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Shiba
authors.affiliation: Mouse epigenetics project, ISS/Kibo experiment, Japan Aerospace Exploration Agency, JAXA, Tsukuba, Japan; Department of Systems BioMedicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Asahara
authors.affiliation: Mouse epigenetics project, ISS/Kibo experiment, Japan Aerospace Exploration Agency, JAXA, Tsukuba, Japan; Laboratory of Developmental Genetics, Center for Experimental Medicine and Systems Biology, The University of Tokyo, Tokyo, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Yoshida
authors.affiliation: Mouse epigenetics project, ISS/Kibo experiment, Japan Aerospace Exploration Agency, JAXA, Tsukuba, Japan; Laboratory Animal Resource Center, University of Tsukuba, Tsukuba, Ibaraki, Japan; Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Mouse epigenetics project, ISS/Kibo experiment, Japan Aerospace Exploration Agency, JAXA, Tsukuba, Japan; Department of Physiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Morita
authors.affiliation: Division of Cellular and Molecular Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Mouse epigenetics project, ISS/Kibo experiment, Japan Aerospace Exploration Agency, JAXA, Tsukuba, Japan.
authors.forename: Taishin
authors.initials: T
authors.lastname: Akiyama
mesh_terms: D000818:Animals; D015415:Biomarkers; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002452:Cell Count; D004847:Epithelial Cells / Q000378:metabolism*; D015870:Gene Expression; D018471:Hypergravity; D016130:Immunophenotyping; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000378:metabolism*; D060168:Thymocytes / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology* / Q000378:metabolism*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D015704:CD4 Antigens; D016827:CD8 Antigens; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B