Scientific Reports (Jul 2019)

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 Murakami,
  • Toshio Hirano

DOI
https://doi.org/10.1038/s41598-019-47132-5
Journal volume & issue
Vol. 9, no. 1
pp. 1 – 14

Abstract

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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.