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

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 MurakamiToshio Hirano

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4 Citations (Scopus)

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.

Original languageEnglish
Article number10842
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

ASJC Scopus subject areas

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    Nishida, K., Hasegawa, A., Yamasaki, S., Uchida, R., Ohashi, W., Kurashima, Y., Kunisawa, J., Kimura, S., Iwanaga, T., Watarai, H., Hase, K., Ogura, H., Nakayama, M., Kashiwakura, J. I., Okayama, Y., Kubo, M., Ohara, O., Kiyono, H., Koseki, H., ... Hirano, T. (2019). Mast cells play role in wound healing through the ZnT2/GPR39/IL-6 axis. Scientific reports, 9(1), [10842]. https://doi.org/10.1038/s41598-019-47132-5