芳香烃受体在治疗免疫炎症性皮肤病中的应用和新药开发

Aryl hydrocarbons receptor in the treatment of immune inflammatory skin diseases and drug development

芳香烃受体(AhR)作为环境⁃细胞相互作用的传感器,在维持皮肤屏障功能、皮肤免疫系统和抗氧化过程中起着重要作用,并能调控许多皮肤基本功能相关的基因表达。AhR在所有的皮肤细胞类型中均有较高水平的表达,参与了包括特应性皮炎和银屑病在内的多种炎症性皮肤病的进展。由于AhR蛋白结构的复杂性,长期以来其晶体结构一直未能成功解析,近期研究人员获得了靛红和HSP90⁃XAP2⁃AhR复合物结合的晶体结构。临床研究表明通过配体激活AhR通路,对炎症性皮肤疾病的治疗具有意义,AhR激动剂本维莫德在银屑病的临床治疗中获得成功已经证明了这一点。本文综述了AhR在炎症性皮肤病中的作用和目前的新药开发进展。

As a sensor of environment⁃cell interaction,aryl hydrocarbon receptor(AhR)plays an important role in maintaining barrier function,immune system and antioxidant process of the skin.AhR regulates the expression of many genes that are related to basic skin functions.It is expressed in all types of skin cells and involved in the progression of a variety of inflammatory skin diseases,including atopic dermatitis and psoriasis.Due to the complexity of the AhR protein structure,its crystal structure has not been successfully resolved until researchers obtained the crystal structure of indirubin binding to HSP90⁃XAP2⁃AhR complex recently.Clinical studies have shown that activation of the AhR pathway by ligands is of significance to the treatment of inflammatory skin diseases,as demonstrated by the clinical success of an AhR agonist,Benvitimod,for the treatment of psoriasis.This article presents a brief review on the role of AhR in inflammatory skin diseases and the current progress in drug development.