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

Tateishi R, Akiyama N, Miyauchi M, Yoshinaga R, Sasanuma H, Kudo T, Shimbo M, Shinohara M, Obata K, Inoue J, Shirakawa M, Shiba D, Asahara H, Yoshida N, Takahashi S, Morita H, Akiyama T - PLoS ONE (2015)

Bottom Line: We investigated the effects of hypergravity (2G) on murine thymic cells.Interestingly, a surgical lesion of the inner ear's vestibular apparatus inhibited these hypergravity effects.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

Increment of keratin-5 keratin-8-double positive cells induced by hypergravity is persistent.Immunostaining of thymic section from mice exposed to 2 g gravity (2G) for 14 days. Thymic frozen sections were immunostained with a combination of anti-keratin-8 antibodies (upper panels) and anti-keratin-5 (middle panels). Merged images are shown in lower panels. Mice were exposed to 2 g gravity (2G) for 3 days or left under 1G (Control). Vestibular apparatus are surgically disrupted in some groups of mice (VL). Data are representatives of 6 independent mice samples (N = 6). Scale bars indicate 100 μm. Data are representatives of 3 independent mice samples (N = 3).
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pone.0141650.g006: Increment of keratin-5 keratin-8-double positive cells induced by hypergravity is persistent.Immunostaining of thymic section from mice exposed to 2 g gravity (2G) for 14 days. Thymic frozen sections were immunostained with a combination of anti-keratin-8 antibodies (upper panels) and anti-keratin-5 (middle panels). Merged images are shown in lower panels. Mice were exposed to 2 g gravity (2G) for 3 days or left under 1G (Control). Vestibular apparatus are surgically disrupted in some groups of mice (VL). Data are representatives of 6 independent mice samples (N = 6). Scale bars indicate 100 μm. Data are representatives of 3 independent mice samples (N = 3).

Mentions: We further investigated the maintenance of TECs in mice exposed to long-term 2G. Flow cytometric analysis showed that the percentages of mTEC and UEA-1–CD80lo TEC fractions in total TECs were not practically altered in the thymus exposed to 2G for 14 days (Fig 5A). However, the cell numbers of mTEChi were significantly reduced by 2G exposure for 14 days (Fig 5B). In addition, although the reduction was not statistically significant, the numbers of other cell fractions were slightly decreased (Fig 5B). In contrast to practically complete recovery of DP, these data suggest that 2G exposure persistently reduces the number of mature mTECs and probably also reduces other TECs. VL itself appears to cause a reduction in the percentage of UEA-1–CD80lo TEC fraction and the total TEC numbers for unknown reasons (Fig 5A and 5B). However, it should be noted that 2G-dependency was not evident in TEC of VL mice. An immunohistochemical study suggests that the 2G-dependent increment of K5+K8+ TECs persistently occurred in the thymus of mice exposed to 2G for 14 days, even though the effect appears milder than that of short-term 2G exposure (Fig 6). Similar to the effect of short-term 2G, the increment of K5+K8+ by long-term 2G exposure was practically absent in the VL mice (Fig 6).


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

Tateishi R, Akiyama N, Miyauchi M, Yoshinaga R, Sasanuma H, Kudo T, Shimbo M, Shinohara M, Obata K, Inoue J, Shirakawa M, Shiba D, Asahara H, Yoshida N, Takahashi S, Morita H, Akiyama T - PLoS ONE (2015)

Increment of keratin-5 keratin-8-double positive cells induced by hypergravity is persistent.Immunostaining of thymic section from mice exposed to 2 g gravity (2G) for 14 days. Thymic frozen sections were immunostained with a combination of anti-keratin-8 antibodies (upper panels) and anti-keratin-5 (middle panels). Merged images are shown in lower panels. Mice were exposed to 2 g gravity (2G) for 3 days or left under 1G (Control). Vestibular apparatus are surgically disrupted in some groups of mice (VL). Data are representatives of 6 independent mice samples (N = 6). Scale bars indicate 100 μm. Data are representatives of 3 independent mice samples (N = 3).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4626100&req=5

pone.0141650.g006: Increment of keratin-5 keratin-8-double positive cells induced by hypergravity is persistent.Immunostaining of thymic section from mice exposed to 2 g gravity (2G) for 14 days. Thymic frozen sections were immunostained with a combination of anti-keratin-8 antibodies (upper panels) and anti-keratin-5 (middle panels). Merged images are shown in lower panels. Mice were exposed to 2 g gravity (2G) for 3 days or left under 1G (Control). Vestibular apparatus are surgically disrupted in some groups of mice (VL). Data are representatives of 6 independent mice samples (N = 6). Scale bars indicate 100 μm. Data are representatives of 3 independent mice samples (N = 3).
Mentions: We further investigated the maintenance of TECs in mice exposed to long-term 2G. Flow cytometric analysis showed that the percentages of mTEC and UEA-1–CD80lo TEC fractions in total TECs were not practically altered in the thymus exposed to 2G for 14 days (Fig 5A). However, the cell numbers of mTEChi were significantly reduced by 2G exposure for 14 days (Fig 5B). In addition, although the reduction was not statistically significant, the numbers of other cell fractions were slightly decreased (Fig 5B). In contrast to practically complete recovery of DP, these data suggest that 2G exposure persistently reduces the number of mature mTECs and probably also reduces other TECs. VL itself appears to cause a reduction in the percentage of UEA-1–CD80lo TEC fraction and the total TEC numbers for unknown reasons (Fig 5A and 5B). However, it should be noted that 2G-dependency was not evident in TEC of VL mice. An immunohistochemical study suggests that the 2G-dependent increment of K5+K8+ TECs persistently occurred in the thymus of mice exposed to 2G for 14 days, even though the effect appears milder than that of short-term 2G exposure (Fig 6). Similar to the effect of short-term 2G, the increment of K5+K8+ by long-term 2G exposure was practically absent in the VL mice (Fig 6).

Bottom Line: We investigated the effects of hypergravity (2G) on murine thymic cells.Interestingly, a surgical lesion of the inner ear's vestibular apparatus inhibited these hypergravity effects.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus