PDF(Pubmed)
Abstract：
The transmembrane glycoprotein OX40 receptor (OX40) and its ligand, OX40L, are instrumental modulators of the adaptive immune response in humans. OX40 functions as a costimulatory molecule that promotes T cell activation, differentiation, and survival through ligation with OX40L. T cells play an integral role in the pathogenesis of several inflammatory skin conditions, including atopic dermatitis (AD). In particular, T helper 2 (TH2) cells strongly contribute to AD pathogenesis via the production of cytokines associated with type 2 inflammation (e.g., IL-4, IL-5, IL-13, and IL-31) that lead to skin barrier dysfunction and pruritus. The OX40-OX40L interaction also promotes the activation and proliferation of other T helper cell populations (e.g., TH1, TH22, and TH17), and AD patients have demonstrated higher levels of OX40 expression on peripheral blood mononuclear cells than healthy controls. As such, the OX40-OX40L pathway is a potential target for AD treatment. Novel therapies targeting the OX40 pathway are currently in development, several of which have demonstrated promising safety and efficacy results in patients with moderate-to-severe AD. Herein, we review the function of OX40 and the OX40-OX40L signaling pathway, their role in AD pathogenesis, and emerging therapies targeting OX40-OX40L that may offer insights into the future of AD management.
摘要：
跨膜糖蛋白OX40受体(OX40)及其配体,OX40L,是人类适应性免疫反应的仪器调节剂。OX40作为促进T细胞活化的共刺激分子，分化,和通过与OX40L连接存活。T细胞在几种炎性皮肤病的发病机理中起着不可或缺的作用，包括特应性皮炎（AD）。特别是,辅助性T细胞2（TH2）细胞通过产生与2型炎症相关的细胞因子强烈促进AD发病机理（例如，导致皮肤屏障功能障碍和瘙痒的IL-4，IL-5，IL-13和IL-31）。OX40-OX40L相互作用还促进其他T辅助细胞群的激活和增殖（例如，TH1、TH22和TH17），和AD患者在外周血单核细胞上的OX40表达水平高于健康对照。因此，OX40-OX40L通路是AD治疗的潜在靶点。目前正在开发针对OX40途径的新疗法，其中一些已证明在中度至重度AD患者中具有良好的安全性和有效性。在这里，我们综述了OX40的功能和OX40-OX40L信号通路,它们在AD发病机制中的作用，以及针对OX40-OX40L的新兴疗法，可能为AD管理的未来提供见解。
