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PLoS One. 2015 Oct 29;10(10):e0141650. doi: 10.1371/journal.pone.0141650. eCollection 2015.

Hypergravity Provokes a Temporary Reduction in CD4+CD8+ Thymocyte Number and a Persistent Decrease in Medullary Thymic Epithelial Cell Frequency in Mice.

Author information

1
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.
2
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.
3
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.
4
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.
5
Mouse epigenetics project, ISS/Kibo experiment, Japan Aerospace Exploration Agency, JAXA, Tsukuba, Japan; Department of Physiology, Gifu University Graduate School of Medicine, Gifu, Japan.
6
Division of Cellular and Molecular Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
7
Mouse epigenetics project, ISS/Kibo experiment, Japan Aerospace Exploration Agency, JAXA, Tsukuba, Japan; JEM Utilization Center, Human Spaceflight Technology Directorate, JAXA, Tsukuba, Ibaraki, Japan.
8
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.

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.

PMID:
26513242
PMCID:
PMC4626100
DOI:
10.1371/journal.pone.0141650
[Indexed for MEDLINE]
Free PMC Article

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