Wang Yangping, Bai Yang, Li Yashu, Liang Guangping, Jiang Yufeng, Liu Zhongyang, Liu Meixi, Hao Jianlei, Zhang Xiaorong, Hu Xiaohong, Chen Jian, Wang Rupeng, Yin Zhinan, Wu Jun, Luo Gaoxing, He Weifeng
State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, The Third Military Medical University, Chongqing, China.
Wound Healing Center, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, China.
Front Immunol. 2017 Nov 24;8:1557. doi: 10.3389/fimmu.2017.01557. eCollection 2017.
Altered homeostasis and dysfunction of dendritic epidermal T cells (DETCs) contribute to abnormal diabetic wound healing. IL-15 plays important roles in survival and activation of T lymphocytes. Recently, reduction of epidermal IL-15 has been reported as an important mechanism for abnormal DETC homeostasis in streptozotocin -induced diabetic animals. However, the role of IL-15 in impaired diabetic wound healing remains unknown. Here, we found that, through rescuing the insufficient activation of DETCs, IL-15 increased IGF-1 production by DETCs and thereby promoted diabetic skin wound repair. Regulation of IGF-1 in DETCs by IL-15 was partly dependent on the mTOR pathway. In addition, expression of IL-15 and IGF-1 were positively correlated in wounded epidermis. Together, our data indicated that IL-15 enhanced IGF-1 production by DETCs to promoting diabetic wound repair, suggesting IL-15 as a potential therapeutic agent for managing diabetic wound healing.
树突状表皮T细胞(DETCs)的内环境稳态改变和功能障碍导致糖尿病伤口愈合异常。白细胞介素-15(IL-15)在T淋巴细胞的存活和激活中起重要作用。最近,有报道称表皮IL-15减少是链脲佐菌素诱导的糖尿病动物中DETCs内环境稳态异常的重要机制。然而,IL-15在糖尿病伤口愈合受损中的作用仍不清楚。在此,我们发现,通过挽救DETCs的激活不足,IL-15增加了DETCs产生的胰岛素样生长因子-1(IGF-1),从而促进糖尿病皮肤伤口修复。IL-15对DETCs中IGF-1的调节部分依赖于雷帕霉素靶蛋白(mTOR)途径。此外,IL-15和IGF-1的表达在受伤表皮中呈正相关。总之,我们的数据表明,IL-15通过增加DETCs产生IGF-1来促进糖尿病伤口修复,提示IL-15作为治疗糖尿病伤口愈合的潜在药物。