Role of the p63-FoxN1 regulatory axis in thymic epithelial cell homeostasis during aging

The p63 gene regulates thymic epithelial cell (TEC) proliferation, whereas FoxN1 regulates their differentiation. However, their collaborative role in the regulation of TEC homeostasis during thymic aging is largely unknown. In murine models, the proportion of TAp63+, but not ΔNp63+, TECs was increa...

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Main Authors:	Burnley, P, Rahman, M, Wang, H, Zhang, Z, Sun, X, Zhuge, Q, Su, D-M
Format:	Online
Language:	English
Published:	Nature Publishing Group 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3847336/

id	pubmed-3847336
recordtype	oai_dc
spelling	pubmed-38473362013-12-03 Role of the p63-FoxN1 regulatory axis in thymic epithelial cell homeostasis during aging Burnley, P Rahman, M Wang, H Zhang, Z Sun, X Zhuge, Q Su, D-M Original Article The p63 gene regulates thymic epithelial cell (TEC) proliferation, whereas FoxN1 regulates their differentiation. However, their collaborative role in the regulation of TEC homeostasis during thymic aging is largely unknown. In murine models, the proportion of TAp63+, but not ΔNp63+, TECs was increased with age, which was associated with an age-related increase in senescent cell clusters, characterized by SA-β-Gal+ and p21+ cells. Intrathymic infusion of exogenous TAp63 cDNA into young wild-type (WT) mice led to an increase in senescent cell clusters. Blockade of TEC differentiation via conditional FoxN1 gene knockout accelerated the appearance of this phenotype to early middle age, whereas intrathymic infusion of exogenous FoxN1 cDNA into aged WT mice brought only a modest reduction in the proportion of TAp63+ TECs, but an increase in ΔNp63+ TECs in the partially rejuvenated thymus. Meanwhile, we found that the increased TAp63+ population contained a high proportion of phosphorylated-p53 TECs, which may be involved in the induction of cellular senescence. Thus, TAp63 levels are positively correlated with TEC senescence but inversely correlated with expression of FoxN1 and FoxN1-regulated TEC differentiation. Thereby, the p63-FoxN1 regulatory axis in regulation of postnatal TEC homeostasis has been revealed. Nature Publishing Group 2013-11 2013-11-21 /pmc/articles/PMC3847336/ /pubmed/24263106 http://dx.doi.org/10.1038/cddis.2013.460 Text en Copyright © 2013 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Burnley, P Rahman, M Wang, H Zhang, Z Sun, X Zhuge, Q Su, D-M
spellingShingle	Burnley, P Rahman, M Wang, H Zhang, Z Sun, X Zhuge, Q Su, D-M Role of the p63-FoxN1 regulatory axis in thymic epithelial cell homeostasis during aging
author_facet	Burnley, P Rahman, M Wang, H Zhang, Z Sun, X Zhuge, Q Su, D-M
author_sort	Burnley, P
title	Role of the p63-FoxN1 regulatory axis in thymic epithelial cell homeostasis during aging
title_short	Role of the p63-FoxN1 regulatory axis in thymic epithelial cell homeostasis during aging
title_full	Role of the p63-FoxN1 regulatory axis in thymic epithelial cell homeostasis during aging
title_fullStr	Role of the p63-FoxN1 regulatory axis in thymic epithelial cell homeostasis during aging
title_full_unstemmed	Role of the p63-FoxN1 regulatory axis in thymic epithelial cell homeostasis during aging
title_sort	role of the p63-foxn1 regulatory axis in thymic epithelial cell homeostasis during aging
description	The p63 gene regulates thymic epithelial cell (TEC) proliferation, whereas FoxN1 regulates their differentiation. However, their collaborative role in the regulation of TEC homeostasis during thymic aging is largely unknown. In murine models, the proportion of TAp63+, but not ΔNp63+, TECs was increased with age, which was associated with an age-related increase in senescent cell clusters, characterized by SA-β-Gal+ and p21+ cells. Intrathymic infusion of exogenous TAp63 cDNA into young wild-type (WT) mice led to an increase in senescent cell clusters. Blockade of TEC differentiation via conditional FoxN1 gene knockout accelerated the appearance of this phenotype to early middle age, whereas intrathymic infusion of exogenous FoxN1 cDNA into aged WT mice brought only a modest reduction in the proportion of TAp63+ TECs, but an increase in ΔNp63+ TECs in the partially rejuvenated thymus. Meanwhile, we found that the increased TAp63+ population contained a high proportion of phosphorylated-p53 TECs, which may be involved in the induction of cellular senescence. Thus, TAp63 levels are positively correlated with TEC senescence but inversely correlated with expression of FoxN1 and FoxN1-regulated TEC differentiation. Thereby, the p63-FoxN1 regulatory axis in regulation of postnatal TEC homeostasis has been revealed.
publisher	Nature Publishing Group
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3847336/
_version_	1612032969457795072

Role of the p63-FoxN1 regulatory axis in thymic epithelial cell homeostasis during aging

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