Department of Microbial Chemistry, Kobe Pharmaceutical University, Kobe, Japan.
Department of Molecular Medicine and Metabolism, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.
Sci Rep. 2017 Mar 23;7(1):330. doi: 10.1038/s41598-017-00349-8.
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.
我们之前已经表明，成纤维细胞生长因子 21（Fgf21）在胸腺和肝脏中表达。根据这种表达谱，最近有报道称 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，发现年轻的 Fgf21 敲除小鼠，而不是β-Klotho 敲除小鼠或成年 Fgf21 敲除小鼠，CD4 和 CD8 单阳性胸腺细胞的百分比明显减少，而 TEC 没有明显改变。此外，重组 FGF21 蛋白的治疗挽救了 Fgf21 敲除小鼠胎儿胸腺器官培养（FTOC）的损伤。Annexin V 染色显示 FGF21 蛋白增强了 FTOC 中正在进行选择过程的未成熟胸腺细胞的凋亡，表明 FGF21 可能有助于发育中的 T 细胞的选择。代谢刺激诱导的肝脏内分泌 Fgf21 不会影响幼年胸腺细胞的发育。我们的数据表明，Fgf21 在新生儿和幼年胸腺中作为一种胸腺内细胞因子发挥作用，以β-Klotho 非依赖的方式参与胸腺细胞的发育。
