Hypergravity Provokes a Temporary Reduction in CD4+CD8+ Thymocyte Number and a Persistent Decrease in Medullary Thymic Epithelial Cell Frequency in Mice.
Hypergravity Provokes a Temporary Reduction in CD4+CD8+ Thymocyte Number and a Persistent Decrease in Medullary Thymic Epithelial Cell Frequency in Mice.
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DOI：
10.1371/journal.pone.0141650
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Akiyama T
中科院分区：
文献类型：
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作者：
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
重力变化影响许多免疫系统。我们研究了超重力（2G）对小鼠胸腺细胞的影响。将小鼠暴露于 2G 三天，降低了 CD4+CD8+ 胸腺细胞 (DP) 和成熟髓质胸腺上皮细胞 (mTEC) 的频率，同时伴随着角蛋白 5 和角蛋白 8 双阳性 (K5+K8+) TEC 的增加，据报道，这些 TEC 含有 TEC 祖细胞。虽然 DP 的减少通过 2G 暴露 14 天得以恢复，但成熟 mTEC 的减少和 K5+K8+ TEC 的增加仍然存在。有趣的是，内耳前庭器官的手术损伤抑制了这些超重力效应。定量 PCR 分析显示，对 mTEC 功能和发育至关重要的 Aire 和 RANK 基因表达在 2G 暴露 3 天后上调，随后在 2G 暴露 14 天后下调。出乎意料的是，mTEC 基因表达的这种动态变化与前庭器官无关。总体而言，数据表明，2G 以前庭系统依赖性方式导致 DP 暂时减少和成熟 mTEC 持续减少，并且还会在不涉及前庭系统的情况下失调 mTEC 基因表达。这些数据可能有助于了解太空飞行和生活期间重力变化对胸腺功能的影响。
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.