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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers
  • CD4 Antigens / metabolism
  • CD8 Antigens / metabolism
  • Cell Count*
  • Epithelial Cells / metabolism*
  • Gene Expression
  • Hypergravity*
  • Immunophenotyping
  • Mice
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptor Activator of Nuclear Factor-kappa B / genetics
  • Receptor Activator of Nuclear Factor-kappa B / metabolism
  • T-Lymphocyte Subsets / metabolism*
  • Thymocytes / metabolism*
  • Thymus Gland / cytology*
  • Thymus Gland / metabolism*
  • Time Factors

Substances

  • Biomarkers
  • CD4 Antigens
  • CD8 Antigens
  • RNA, Messenger
  • Receptor Activator of Nuclear Factor-kappa B

Grant support

This work was supported by Short arm centrifuge project commissioned from JAXA (13YPTK-013584, 4YPTK-000980, and 15YPTK-002009) (H.M.), Prioritized research selected for life science from JAXA (14YPTK-005512)(T.S., H.A., N.Y., and H.M.), a grant from Specially Promoted Project of the Toyota Physical and Chemical Research Institute (T.A.), a grant from Princess Takamatsu Cancer Research Fund (T.A.), Grant-in-Aid for Challenging Exploratory Research (26670234) (T.A.). and Grant-in-Aid for Scientific Research on Innovative Areas (15H01150) (T. A.).