Mast cells play role in wound healing through the ZnT2/GPR39/IL-6 axis
Mast cells play role in wound healing through the ZnT2/GPR39/IL-6 axis
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DOI：
10.1038/s41598-019-47132-5
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发表时间：
2019-07-25
影响因子：
4.6
通讯作者：
Hirano, Toshio
中科院分区：
文献类型：
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作者：
Nishida, Keigo;Hasegawa, Aiko;Hirano, Toshio
锌（Zn）是一种必需营养素，缺乏锌会导致免疫缺陷和皮肤疾病。包括肥大细胞在内的各种细胞在被激活时释放含锌颗粒；然而，释放的锌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，锌转运体ZnT2是必需的锌从肥大细胞释放。此外，我们发现锌和肥大细胞诱导炎症细胞（如皮肤成纤维细胞）产生IL-6，并促进伤口愈合，这一过程涉及炎症。锌通过锌受体GPR39介导的信号通路诱导包括IL-6在内的多种促炎细胞因子的产生。与这些发现一致，缺乏IL-6或GPR39的小鼠伤口愈合受损。因此，我们的研究结果表明，锌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。
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.