Mast cells play role in wound healing through the ZnT2/GPR39/IL-6 axis

Abstract Zinc (Zn) is an essential nutrient and its deficiency causes immunodeficiency and skin disorders. Various cells including mast cells release Zn-containing granules when activated; however, the biological role of the released Zn is currently unclear. Here we report our findings that Zn trans...

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Autores principales:	Keigo Nishida, Aiko Hasegawa, Satoru Yamasaki, Ryota Uchida, Wakana Ohashi, Yosuke Kurashima, Jun Kunisawa, Shunsuke Kimura, Toshihiko Iwanaga, Hiroshi Watarai, Koji Hase, Hideki Ogura, Manabu Nakayama, Jun-ichi Kashiwakura, Yoshimichi Okayama, Masato Kubo, Osamu Ohara, Hiroshi Kiyono, Haruhiko Koseki, Masaaki Murakami, Toshio Hirano
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/90f2f409e35a43b6aaf560abee33b2ff
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spelling	oai:doaj.org-article:90f2f409e35a43b6aaf560abee33b2ff2021-12-02T15:08:21ZMast cells play role in wound healing through the ZnT2/GPR39/IL-6 axis10.1038/s41598-019-47132-52045-2322https://doaj.org/article/90f2f409e35a43b6aaf560abee33b2ff2019-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-47132-5https://doaj.org/toc/2045-2322Abstract Zinc (Zn) is an essential nutrient and its deficiency causes immunodeficiency and skin disorders. Various cells including mast cells release Zn-containing granules when activated; however, the biological role of the released Zn is currently unclear. Here we report our findings that Zn transporter ZnT2 is required for the release of Zn from mast cells. In addition, we found that Zn and mast cells induce IL-6 production from inflammatory cells such as skin fibroblasts and promote wound healing, a process that involves inflammation. Zn induces the production of a variety of pro-inflammatory cytokines including IL-6 through signaling pathways mediated by the Zn receptor GPR39. Consistent with these findings, wound healing was impaired in mice lacking IL-6 or GPR39. Thus, our results show that Zn and mast cells play a critical role in wound healing through activation of the GPR39/IL-6 signaling axis.Keigo NishidaAiko HasegawaSatoru YamasakiRyota UchidaWakana OhashiYosuke KurashimaJun KunisawaShunsuke KimuraToshihiko IwanagaHiroshi WataraiKoji HaseHideki OguraManabu NakayamaJun-ichi KashiwakuraYoshimichi OkayamaMasato KuboOsamu OharaHiroshi KiyonoHaruhiko KosekiMasaaki MurakamiToshio HiranoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-14 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Keigo Nishida Aiko Hasegawa Satoru Yamasaki Ryota Uchida Wakana Ohashi Yosuke Kurashima Jun Kunisawa Shunsuke Kimura Toshihiko Iwanaga Hiroshi Watarai Koji Hase Hideki Ogura Manabu Nakayama Jun-ichi Kashiwakura Yoshimichi Okayama Masato Kubo Osamu Ohara Hiroshi Kiyono Haruhiko Koseki Masaaki Murakami Toshio Hirano Mast cells play role in wound healing through the ZnT2/GPR39/IL-6 axis
description	Abstract Zinc (Zn) is an essential nutrient and its deficiency causes immunodeficiency and skin disorders. Various cells including mast cells release Zn-containing granules when activated; however, the biological role of the released Zn is currently unclear. Here we report our findings that Zn transporter ZnT2 is required for the release of Zn from mast cells. In addition, we found that Zn and mast cells induce IL-6 production from inflammatory cells such as skin fibroblasts and promote wound healing, a process that involves inflammation. Zn induces the production of a variety of pro-inflammatory cytokines including IL-6 through signaling pathways mediated by the Zn receptor GPR39. Consistent with these findings, wound healing was impaired in mice lacking IL-6 or GPR39. Thus, our results show that Zn and mast cells play a critical role in wound healing through activation of the GPR39/IL-6 signaling axis.
format	article
author	Keigo Nishida Aiko Hasegawa Satoru Yamasaki Ryota Uchida Wakana Ohashi Yosuke Kurashima Jun Kunisawa Shunsuke Kimura Toshihiko Iwanaga Hiroshi Watarai Koji Hase Hideki Ogura Manabu Nakayama Jun-ichi Kashiwakura Yoshimichi Okayama Masato Kubo Osamu Ohara Hiroshi Kiyono Haruhiko Koseki Masaaki Murakami Toshio Hirano
author_facet	Keigo Nishida Aiko Hasegawa Satoru Yamasaki Ryota Uchida Wakana Ohashi Yosuke Kurashima Jun Kunisawa Shunsuke Kimura Toshihiko Iwanaga Hiroshi Watarai Koji Hase Hideki Ogura Manabu Nakayama Jun-ichi Kashiwakura Yoshimichi Okayama Masato Kubo Osamu Ohara Hiroshi Kiyono Haruhiko Koseki Masaaki Murakami Toshio Hirano
author_sort	Keigo Nishida
title	Mast cells play role in wound healing through the ZnT2/GPR39/IL-6 axis
title_short	Mast cells play role in wound healing through the ZnT2/GPR39/IL-6 axis
title_full	Mast cells play role in wound healing through the ZnT2/GPR39/IL-6 axis
title_fullStr	Mast cells play role in wound healing through the ZnT2/GPR39/IL-6 axis
title_full_unstemmed	Mast cells play role in wound healing through the ZnT2/GPR39/IL-6 axis
title_sort	mast cells play role in wound healing through the znt2/gpr39/il-6 axis
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/90f2f409e35a43b6aaf560abee33b2ff
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Mast cells play role in wound healing through the ZnT2/GPR39/IL-6 axis

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