Weakened IL-15 Production and Impaired mTOR Activation Alter Dendritic Epidermal T Cell Homeostasis in Diabetic Mice

Abstract Diabetes is associated with impaired wound healing, which may be caused primarily by a deficiency in dendritic epidermal T cells (DETCs). In the epidermis, IL-15, IGF-1, and mTOR are known to regulate the maintenance of DETCs; however, it is unclear how these molecules may intersect to regu...

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Autores principales:	Zhongyang Liu, Guangping Liang, Li Gui, Yashu Li, Meixi Liu, Yang bai, Xiaorong Zhang, Xiaohong Hu, Jian Chen, Chibing Huang, Xusheng Liu, Gaoxing Luo, Jun Wu, Weifeng He
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3793b5cbdd7d42b6b9deabcb127a2af1
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spelling	oai:doaj.org-article:3793b5cbdd7d42b6b9deabcb127a2af12021-12-02T16:07:00ZWeakened IL-15 Production and Impaired mTOR Activation Alter Dendritic Epidermal T Cell Homeostasis in Diabetic Mice10.1038/s41598-017-05950-52045-2322https://doaj.org/article/3793b5cbdd7d42b6b9deabcb127a2af12017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05950-5https://doaj.org/toc/2045-2322Abstract Diabetes is associated with impaired wound healing, which may be caused primarily by a deficiency in dendritic epidermal T cells (DETCs). In the epidermis, IL-15, IGF-1, and mTOR are known to regulate the maintenance of DETCs; however, it is unclear how these molecules may intersect to regulate DETC homeostasis in diabetes. Here, we show that the reduction of DETCs in the epidermis of diabetic mice is caused by altered homeostasis mediated by a reduction in IL-15 levels. Both impaired mTOR activation and reduction of IL-15 in the epidermis play important roles in DETC homeostasis. Moreover, IGF-1 drives keratinocytes to produce IL-15. The activation of IL-15 is dependent on mTOR, and conversely, mTOR regulates IGF-1 production in DETC, in a classic feedback regulatory loop. Our data suggest that in the setting of diabetes, reduced IGF-1, impaired mTOR pathway activation and reduced IL-15 in the epidermis function coordinately to promote altered DETC homeostasis and delayed skin wound closure.Zhongyang LiuGuangping LiangLi GuiYashu LiMeixi LiuYang baiXiaorong ZhangXiaohong HuJian ChenChibing HuangXusheng LiuGaoxing LuoJun WuWeifeng HeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Zhongyang Liu Guangping Liang Li Gui Yashu Li Meixi Liu Yang bai Xiaorong Zhang Xiaohong Hu Jian Chen Chibing Huang Xusheng Liu Gaoxing Luo Jun Wu Weifeng He Weakened IL-15 Production and Impaired mTOR Activation Alter Dendritic Epidermal T Cell Homeostasis in Diabetic Mice
description	Abstract Diabetes is associated with impaired wound healing, which may be caused primarily by a deficiency in dendritic epidermal T cells (DETCs). In the epidermis, IL-15, IGF-1, and mTOR are known to regulate the maintenance of DETCs; however, it is unclear how these molecules may intersect to regulate DETC homeostasis in diabetes. Here, we show that the reduction of DETCs in the epidermis of diabetic mice is caused by altered homeostasis mediated by a reduction in IL-15 levels. Both impaired mTOR activation and reduction of IL-15 in the epidermis play important roles in DETC homeostasis. Moreover, IGF-1 drives keratinocytes to produce IL-15. The activation of IL-15 is dependent on mTOR, and conversely, mTOR regulates IGF-1 production in DETC, in a classic feedback regulatory loop. Our data suggest that in the setting of diabetes, reduced IGF-1, impaired mTOR pathway activation and reduced IL-15 in the epidermis function coordinately to promote altered DETC homeostasis and delayed skin wound closure.
format	article
author	Zhongyang Liu Guangping Liang Li Gui Yashu Li Meixi Liu Yang bai Xiaorong Zhang Xiaohong Hu Jian Chen Chibing Huang Xusheng Liu Gaoxing Luo Jun Wu Weifeng He
author_facet	Zhongyang Liu Guangping Liang Li Gui Yashu Li Meixi Liu Yang bai Xiaorong Zhang Xiaohong Hu Jian Chen Chibing Huang Xusheng Liu Gaoxing Luo Jun Wu Weifeng He
author_sort	Zhongyang Liu
title	Weakened IL-15 Production and Impaired mTOR Activation Alter Dendritic Epidermal T Cell Homeostasis in Diabetic Mice
title_short	Weakened IL-15 Production and Impaired mTOR Activation Alter Dendritic Epidermal T Cell Homeostasis in Diabetic Mice
title_full	Weakened IL-15 Production and Impaired mTOR Activation Alter Dendritic Epidermal T Cell Homeostasis in Diabetic Mice
title_fullStr	Weakened IL-15 Production and Impaired mTOR Activation Alter Dendritic Epidermal T Cell Homeostasis in Diabetic Mice
title_full_unstemmed	Weakened IL-15 Production and Impaired mTOR Activation Alter Dendritic Epidermal T Cell Homeostasis in Diabetic Mice
title_sort	weakened il-15 production and impaired mtor activation alter dendritic epidermal t cell homeostasis in diabetic mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/3793b5cbdd7d42b6b9deabcb127a2af1
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Weakened IL-15 Production and Impaired mTOR Activation Alter Dendritic Epidermal T Cell Homeostasis in Diabetic Mice

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