Laboratory of Immune Regulation, Graduate School of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3 Minamitamagaki-cho, Suzuka, Mie, 513-8670, Japan.
Laboratory for Homeostatic Network, RIKEN Center for Integrative Medical Sciences (IMS), 1-7-22 Suehiro-cho, Tsurumi, Yokohama, Kanagawa, 230-0045, Japan.
Sci Rep. 2019 Jul 25;9(1):10842. doi: 10.1038/s41598-019-47132-5.
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.
锌（Zn）是一种必需的营养物质，其缺乏会导致免疫功能缺陷和皮肤疾病。各种细胞包括肥大细胞在被激活时会释放含有 Zn 的颗粒；然而，释放的 Zn 的生物学作用目前尚不清楚。在这里，我们报告了我们的发现，即 Zn 转运蛋白 ZnT2 是肥大细胞释放 Zn 所必需的。此外，我们还发现 Zn 和肥大细胞诱导皮肤成纤维细胞等炎症细胞产生白细胞介素-6（IL-6），并促进涉及炎症的伤口愈合过程。Zn 通过 Zn 受体 GPR39 介导的信号通路诱导多种促炎细胞因子的产生，包括 IL-6。与这些发现一致的是，缺乏 IL-6 或 GPR39 的小鼠的伤口愈合受损。因此，我们的研究结果表明，Zn 和肥大细胞通过激活 GPR39/IL-6 信号轴在伤口愈合中发挥关键作用。
