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

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 Zn...

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Bibliographic Details
Published in:Scientific reports 2019-07, Vol.9 (1), p.10842-14, Article 10842
Main Authors: Nishida, Keigo, Hasegawa, Aiko, Yamasaki, Satoru, Uchida, Ryota, Ohashi, Wakana, Kurashima, Yosuke, Kunisawa, Jun, Kimura, Shunsuke, Iwanaga, Toshihiko, Watarai, Hiroshi, Hase, Koji, Ogura, Hideki, Nakayama, Manabu, Kashiwakura, Jun-ichi, Okayama, Yoshimichi, Kubo, Masato, Ohara, Osamu, Kiyono, Hiroshi, Koseki, Haruhiko, Murakami, Masaaki, Hirano, Toshio
Format: Article
Language:English
Subjects:
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38/89
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631/80
64/60
96/1
96/21
96/31
96/63
96/95
Animals
Cation Transport Proteins - metabolism
Cell Line
Cells, Cultured
Fibroblasts
Granule cells
Histamine
Humanities and Social Sciences
Immunodeficiency
Inflammation
Interleukin 6
Interleukin-6 - metabolism
Mast cells
Mast Cells - cytology
Mast Cells - metabolism
Mice
multidisciplinary
Receptors, G-Protein-Coupled - metabolism
Science
Science (multidisciplinary)
Wound healing
Wound Healing - physiology
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-019-47132-5