Fgf21 regulates T-cell development in the neonatal and juvenile thymus.
Fgf21 regulates T-cell development in the neonatal and juvenile thymus.
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DOI：
10.1038/s41598-017-00349-8
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发表时间：
2017-03-23
影响因子：
4.6
通讯作者：
Konishi M
中科院分区：
文献类型：
--
作者：
Nakayama Y;Masuda Y;Ohta H;Tanaka T;Washida M;Nabeshima YI;Miyake A;Itoh N;Konishi M
我们之前已经证明成纤维细胞生长因子 21 (Fgf21) 在胸腺和肝脏中表达。与这种表达谱一致，最近报道 Fgf21 通过改善胸腺上皮细胞 (TEC) 的功能来防止与衰老相关的胸腺衰老。然而，Fgf21 在幼年胸腺中的功能仍有待阐明。我们研究了 Fgf21 在幼年胸腺中的生理作用，发现幼年 Fgf21 敲除小鼠（而非 β-Klotho 敲除小鼠和成年 Fgf21 敲除小鼠）表现出单阳性 CD4+ 和 CD8+ 胸腺细胞百分比显着降低，而 TEC 没有明显改变。此外，重组 FGF21 蛋白治疗可挽救 Fgf21 敲除小鼠胎儿胸腺器官培养 (FTOC) 的损伤。膜联蛋白 V 染色显示 FGF21 蛋白增强了 FTOC 中经历选择过程的未成熟胸腺细胞的凋亡，表明 FGF21 可能促进发育中 T 细胞的选择。来自肝脏的内分泌Fgf21通过代谢刺激诱导并不影响幼年胸腺细胞的发育。我们的数据表明，Fgf21 作为新生儿和幼年胸腺中的胸腺内细胞因子之一，以不依赖 β-Klotho 的方式参与胸腺细胞发育。
We have previously shown that Fibroblast growth factor 21 (Fgf21) is expressed in the thymus as well as in the liver. In line with this expression profile, Fgf21 was recently reported to protect against ageing-related thymic senescence by improving the function of thymic epithelial cells (TECs). However, the function of Fgf21 in the juvenile thymus remained to be elucidated. We investigated the physiological roles of Fgf21 in the juvenile thymus and found that young Fgf21 knockout mice, but not β-Klotho knockout mice nor adult Fgf21 knockout mice, showed a significant reduction in the percentage of single-positive CD4+ and CD8+ thymocytes without obvious alteration in TECs. Furthermore, treatment with recombinant FGF21 protein rescued the impairment in fetal thymus organ culture (FTOC) of Fgf21 knockout mice. Annexin V staining revealed FGF21 protein enhanced apoptosis of immature thymocytes undergoing selection process in FTOC, suggesting that FGF21 may facilitate the selection of developing T cells. Endocrine Fgf21 from the liver induced by metabolic stimulation did not affect juvenile thymocyte development. Our data suggest that Fgf21 acts as one of intrathymic cytokines in the neonatal and juvenile thymus, involving thymocyte development in a β-Klotho-independent manner.