Fgf21 regulates T-cell development in the neonatal and juvenile thymus
Abstract 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 (T...
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Nature Portfolio
2017
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oai:doaj.org-article:ab15cf9ac9a2451b8be4e3b3c081e6232021-12-02T15:05:02ZFgf21 regulates T-cell development in the neonatal and juvenile thymus10.1038/s41598-017-00349-82045-2322https://doaj.org/article/ab15cf9ac9a2451b8be4e3b3c081e6232017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00349-8https://doaj.org/toc/2045-2322Abstract 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.Yoshiaki NakayamaYuki MasudaHiroya OhtaTomohiro TanakaMiwa WashidaYo-ichi NabeshimaAyumi MiyakeNobuyuki ItohMorichika KonishiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017) |
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Medicine R Science Q Yoshiaki Nakayama Yuki Masuda Hiroya Ohta Tomohiro Tanaka Miwa Washida Yo-ichi Nabeshima Ayumi Miyake Nobuyuki Itoh Morichika Konishi Fgf21 regulates T-cell development in the neonatal and juvenile thymus |
| description |
Abstract 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. |
| format |
article |
| author |
Yoshiaki Nakayama Yuki Masuda Hiroya Ohta Tomohiro Tanaka Miwa Washida Yo-ichi Nabeshima Ayumi Miyake Nobuyuki Itoh Morichika Konishi |
| author_facet |
Yoshiaki Nakayama Yuki Masuda Hiroya Ohta Tomohiro Tanaka Miwa Washida Yo-ichi Nabeshima Ayumi Miyake Nobuyuki Itoh Morichika Konishi |
| author_sort |
Yoshiaki Nakayama |
| title |
Fgf21 regulates T-cell development in the neonatal and juvenile thymus |
| title_short |
Fgf21 regulates T-cell development in the neonatal and juvenile thymus |
| title_full |
Fgf21 regulates T-cell development in the neonatal and juvenile thymus |
| title_fullStr |
Fgf21 regulates T-cell development in the neonatal and juvenile thymus |
| title_full_unstemmed |
Fgf21 regulates T-cell development in the neonatal and juvenile thymus |
| title_sort |
fgf21 regulates t-cell development in the neonatal and juvenile thymus |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/ab15cf9ac9a2451b8be4e3b3c081e623 |
| work_keys_str_mv |
AT yoshiakinakayama fgf21regulatestcelldevelopmentintheneonatalandjuvenilethymus AT yukimasuda fgf21regulatestcelldevelopmentintheneonatalandjuvenilethymus AT hiroyaohta fgf21regulatestcelldevelopmentintheneonatalandjuvenilethymus AT tomohirotanaka fgf21regulatestcelldevelopmentintheneonatalandjuvenilethymus AT miwawashida fgf21regulatestcelldevelopmentintheneonatalandjuvenilethymus AT yoichinabeshima fgf21regulatestcelldevelopmentintheneonatalandjuvenilethymus AT ayumimiyake fgf21regulatestcelldevelopmentintheneonatalandjuvenilethymus AT nobuyukiitoh fgf21regulatestcelldevelopmentintheneonatalandjuvenilethymus AT morichikakonishi fgf21regulatestcelldevelopmentintheneonatalandjuvenilethymus |
| _version_ |
1718388976110272512 |