Thymic homing of activated CD4+ T cells induces degeneration of the thymic epithelium through excessive RANK signaling

Abstract Activated T cells have been shown to be able to recirculate into the thymus from the periphery. The present study was aimed to elucidate the functional consequences of thymic homing of activated T cells upon developing thymocytes and thymic epithelial cells (TEC). In the presence of activat...

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Autores principales:	Chen Yin, Xiao-Yan Pei, Hui Shen, Ya-Nan Gao, Xiu-Yuan Sun, Wei Wang, Qing Ge, Yu Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a91e87881d6f4e9386a58a9691f1b7b7
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spelling	oai:doaj.org-article:a91e87881d6f4e9386a58a9691f1b7b72021-12-02T12:30:12ZThymic homing of activated CD4+ T cells induces degeneration of the thymic epithelium through excessive RANK signaling10.1038/s41598-017-02653-92045-2322https://doaj.org/article/a91e87881d6f4e9386a58a9691f1b7b72017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02653-9https://doaj.org/toc/2045-2322Abstract Activated T cells have been shown to be able to recirculate into the thymus from the periphery. The present study was aimed to elucidate the functional consequences of thymic homing of activated T cells upon developing thymocytes and thymic epithelial cells (TEC). In the presence of activated T cells, especially CD4+ T cells, T cell development was found to be inhibited in thymic organ cultures with markedly reduced cellularity. Thymic transplantation demonstrated that the inhibitory effect was most likely due to a defective microenvironment. As the major component of the thymic stroma, the TEC compartment was severely disturbed after prolonged exposure to the activated T cells. In addition to reduced cell proliferation, TEC differentiation was heavily skewed to the mTEC lineage. Furthermore, we demonstrated that RANKL highly expressed by activated CD4+ T cells was primarily responsible for the detrimental effects. Presumably, excessive RANK signaling drove overproduction of mTECs and possibly exhaustion of epithelial progenitors, thereby facilitating the deterioration of the epithelial structures. These findings not only reveal a novel activity of activated T cells re-entering the thymus, but also provide a new perspective for understanding the mechanism underlying thymic involution.Chen YinXiao-Yan PeiHui ShenYa-Nan GaoXiu-Yuan SunWei WangQing GeYu ZhangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chen Yin Xiao-Yan Pei Hui Shen Ya-Nan Gao Xiu-Yuan Sun Wei Wang Qing Ge Yu Zhang Thymic homing of activated CD4+ T cells induces degeneration of the thymic epithelium through excessive RANK signaling
description	Abstract Activated T cells have been shown to be able to recirculate into the thymus from the periphery. The present study was aimed to elucidate the functional consequences of thymic homing of activated T cells upon developing thymocytes and thymic epithelial cells (TEC). In the presence of activated T cells, especially CD4+ T cells, T cell development was found to be inhibited in thymic organ cultures with markedly reduced cellularity. Thymic transplantation demonstrated that the inhibitory effect was most likely due to a defective microenvironment. As the major component of the thymic stroma, the TEC compartment was severely disturbed after prolonged exposure to the activated T cells. In addition to reduced cell proliferation, TEC differentiation was heavily skewed to the mTEC lineage. Furthermore, we demonstrated that RANKL highly expressed by activated CD4+ T cells was primarily responsible for the detrimental effects. Presumably, excessive RANK signaling drove overproduction of mTECs and possibly exhaustion of epithelial progenitors, thereby facilitating the deterioration of the epithelial structures. These findings not only reveal a novel activity of activated T cells re-entering the thymus, but also provide a new perspective for understanding the mechanism underlying thymic involution.
format	article
author	Chen Yin Xiao-Yan Pei Hui Shen Ya-Nan Gao Xiu-Yuan Sun Wei Wang Qing Ge Yu Zhang
author_facet	Chen Yin Xiao-Yan Pei Hui Shen Ya-Nan Gao Xiu-Yuan Sun Wei Wang Qing Ge Yu Zhang
author_sort	Chen Yin
title	Thymic homing of activated CD4+ T cells induces degeneration of the thymic epithelium through excessive RANK signaling
title_short	Thymic homing of activated CD4+ T cells induces degeneration of the thymic epithelium through excessive RANK signaling
title_full	Thymic homing of activated CD4+ T cells induces degeneration of the thymic epithelium through excessive RANK signaling
title_fullStr	Thymic homing of activated CD4+ T cells induces degeneration of the thymic epithelium through excessive RANK signaling
title_full_unstemmed	Thymic homing of activated CD4+ T cells induces degeneration of the thymic epithelium through excessive RANK signaling
title_sort	thymic homing of activated cd4+ t cells induces degeneration of the thymic epithelium through excessive rank signaling
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/a91e87881d6f4e9386a58a9691f1b7b7
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Thymic homing of activated CD4+ T cells induces degeneration of the thymic epithelium through excessive RANK signaling

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