Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.
Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea; Department of Dermatology, CHA Bundang Medical Center, CHA University, Seongnam, Korea.
J Invest Dermatol. 2019 Aug;139(8):1648-1657.e7. doi: 10.1016/j.jid.2019.01.023. Epub 2019 Feb 6.
Adipokines modulate immune responses and lipid metabolism in allergic disease; however, little is known about their role in the skin barrier and atopic dermatitis (AD). We identified ZAG, an adipokine that regulates lipid mobilization, as a biomarker for AD. ZAG levels were consistently decreased in sera, T cells, and skin in human AD patients compared with healthy controls. ZAG was primarily detected in the stratum corneum along with FLG and LOR. Knockdown of ZAG with short hairpin RNA resulted in decreased FLG and increased TSLP. Topical ZAG treatment in AD mice recovered ZAG expression in the skin and improved AD-like symptoms, transepidermal water loss, and ceramide levels. Furthermore, topical ZAG treatment induced immunoregulatory effects, including reduction of IL-4, IL-17, and IFN-γ and increased Foxp3 in the skin and lymphoid organs. Interestingly, ZAG treatment also recovered decreased levels of ADAM17, an important player in skin barrier function and immune response in AD. Thus, ZAG deficiency is closely related to skin barrier function and the immune abnormalities of AD, and we suggest that restoration of ZAG may be a promising therapeutic option for the treatment of AD.
脂肪细胞因子调节过敏疾病中的免疫反应和脂质代谢；然而，它们在皮肤屏障和特应性皮炎（AD）中的作用知之甚少。我们鉴定出 ZAG，一种调节脂质动员的脂肪细胞因子，是 AD 的生物标志物。与健康对照组相比，AD 患者的血清、T 细胞和皮肤中 ZAG 水平持续降低。ZAG 主要与 FLG 和 LOR 一起存在于角质层中。用短发夹 RNA 敲低 ZAG 导致 FLG 减少和 TSLP 增加。AD 小鼠的局部 ZAG 治疗恢复了皮肤中的 ZAG 表达，并改善了 AD 样症状、经表皮水分流失和神经酰胺水平。此外，局部 ZAG 治疗诱导了免疫调节作用，包括减少皮肤和淋巴器官中的 IL-4、IL-17 和 IFN-γ 以及增加 Foxp3。有趣的是，ZAG 治疗还恢复了 ADAM17 的水平降低，ADAM17 是 AD 中皮肤屏障功能和免疫反应的重要参与者。因此，ZAG 缺乏与皮肤屏障功能和 AD 的免疫异常密切相关，我们建议恢复 ZAG 可能是治疗 AD 的一种有前途的治疗选择。
