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Fgf21 regulates T-cell development in the neonatal and juvenile thymus

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). How...

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Autores principales: Nakayama, Yoshiaki, Masuda, Yuki, Ohta, Hiroya, Tanaka, Tomohiro, Washida, Miwa, Nabeshima, Yo-ichi, Miyake, Ayumi, Itoh, Nobuyuki, Konishi, Morichika
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5428243/
https://www.ncbi.nlm.nih.gov/pubmed/28336912
http://dx.doi.org/10.1038/s41598-017-00349-8
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author Nakayama, Yoshiaki
Masuda, Yuki
Ohta, Hiroya
Tanaka, Tomohiro
Washida, Miwa
Nabeshima, Yo-ichi
Miyake, Ayumi
Itoh, Nobuyuki
Konishi, Morichika
author_facet Nakayama, Yoshiaki
Masuda, Yuki
Ohta, Hiroya
Tanaka, Tomohiro
Washida, Miwa
Nabeshima, Yo-ichi
Miyake, Ayumi
Itoh, Nobuyuki
Konishi, Morichika
author_sort Nakayama, Yoshiaki
collection PubMed
description 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.
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spelling pubmed-54282432017-05-15 Fgf21 regulates T-cell development in the neonatal and juvenile thymus Nakayama, Yoshiaki Masuda, Yuki Ohta, Hiroya Tanaka, Tomohiro Washida, Miwa Nabeshima, Yo-ichi Miyake, Ayumi Itoh, Nobuyuki Konishi, Morichika Sci Rep Article 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. Nature Publishing Group UK 2017-03-23 /pmc/articles/PMC5428243/ /pubmed/28336912 http://dx.doi.org/10.1038/s41598-017-00349-8 Text en © The Author(s) 2017 This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Nakayama, Yoshiaki
Masuda, Yuki
Ohta, Hiroya
Tanaka, Tomohiro
Washida, Miwa
Nabeshima, Yo-ichi
Miyake, Ayumi
Itoh, Nobuyuki
Konishi, Morichika
Fgf21 regulates T-cell development in the neonatal and juvenile thymus
title 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_short Fgf21 regulates T-cell development in the neonatal and juvenile thymus
title_sort fgf21 regulates t-cell development in the neonatal and juvenile thymus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5428243/
https://www.ncbi.nlm.nih.gov/pubmed/28336912
http://dx.doi.org/10.1038/s41598-017-00349-8
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