@article{364fc555d43242508a3e7182b01a85b1,
title = "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 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.",
author = "Keigo Nishida and Aiko Hasegawa and Satoru Yamasaki and Ryota Uchida and Wakana Ohashi and Yosuke Kurashima and Jun Kunisawa and Shunsuke Kimura and Toshihiko Iwanaga and Hiroshi Watarai and Koji Hase and Hideki Ogura and Manabu Nakayama and Kashiwakura, {Jun ichi} and Yoshimichi Okayama and Masato Kubo and Osamu Ohara and Hiroshi Kiyono and Haruhiko Koseki and Masaaki Murakami and Toshio Hirano",
note = "Funding Information: We thank Drs M. Kopf (Max-Planck-Institute of Immunobiology, Germany) and Y. Iwakura (Tokyo University of Science, Japan) for the IL-6-deficient mice. We thank Drs P. Burrows, M. Kato, and H. Kitamura for critical reading and Drs T. Tanaka, T. Kambe, T. Ugajin, S. Hida, and M. Hershfinkel for technical advice and suggestions. We thank members of the RIKEN Center for Integrative Medial Sciences (IMS-RCAI) animal facility for helping to maintenance of various KO mice. This work was supported by Ms. C. Kariya, Materials Characterization Support Unit, Center for Emergent Matter Science RIKEN for the ICP-AES measurements. We thank A. Ito for excellent technical assistance and R. Kimura for secretarial assistance. This work was supported in part by JSPS KAKENHI Grant Numbers JP16K15152 and JP18H05299 (K.N.), the Takeda Science Foundation (K.N.), the Mochida Memorial Foundation for Medical and Pharmaceutical Research (K.N.), and SENSHIN Medical Research Foundation (K.N.). This work was also supported by grants from Japan Agency for Medical Research and Development (H.K.); Japan Society for the Promotion of Science (JSPS), Grant-in Aid for Scientific Research S (H.K.) and Young Scientists A (Y.K.), Challenging Research or (Exploratory) (Y.K.), Leading Initiative for Excellent Young Researchers (LEADER) (Y.K.), Mochida Memorial Foundation for Medical and Pharmaceutical Research (Y.K.), The Takeda Science Foundation (Y.K.), The Uehara Memorial Foundation (Y.K.), GSK Japan Research Grant (Y.K.), Science and Technology Research Partnership for Sustainable Development (SATREPS) (H.K.) and the Chiba University-UC San Diego Center for Mucosal Immunology, Allergy, and Vaccines (H.K.). R.U. was supported by Nagai Memorial Research Scholarship from the Pharmaceutical Society of Japan, and Public Interest Incorporated Foundation Tsukushi Scholarship Research Fund. Publisher Copyright: {\textcopyright} 2019, The Author(s).",
year = "2019",
month = dec,
day = "1",
doi = "10.1038/s41598-019-47132-5",
language = "English",
volume = "9",
journal = "Scientific reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}