TWEAK/Fn14信号在银屑病发病机制中的作用及潜在诊疗策略

银屑病是一种常见的慢性炎症性皮肤病,以角质形成细胞异常增殖与分化为重要特征,并涉及多种炎症因子介导的免疫反应机制。肿瘤坏死因子样细胞凋亡弱诱导剂(tumor necrosis factor-like weak inducer of apoptosis,TWEAK)通过与其受体成纤维细胞生长诱导因子14(fibroblast growth factor-inducible 14,Fn14)结合调控细胞增殖、死亡、分化或迁移,促进血管生成、炎性细胞浸润等。近年研究发现,银屑病炎症微环境下角质形成细胞高表达Fn14,TWEAK/Fn14信号激活后促进细胞增殖及相关炎症反应,某些亚型银屑病患者外周血中TWEAK值升高,且经过治疗后出现不同变化。本文将讨论TWEAK/Fn14信号在银屑病发病机制中的具体作用,并为银屑病的诊断与治疗提供潜在的策略。

TWEAK/Fn14 Activation in the Pathogenesis of Psoriasis and Relevant Diagnostic and Therapeutic Strategies

Psoriasis is a common chronic inflammatory skin disease,characterized by abnormal proliferation and differentiation of keratinocytes.There are many types of inflammatory cytokines involved in the immune responses of psoriasis.As a proinflammatory cytokine,tumor necrosis factor-like weak inducer of apoptosis(TWEAK)acts through engaging the sole receptor fibroblast growth-inducing factor 14(Fn14).TWEAK/Fn14 activation modulates cell proliferation,death,differentiation and migration and enhances angiogenesis and infiltration of inflammatory cells.Recently,it was found that keratinocytes in the inflammatory microenvironment of psoriasis highly express Fn14 and TWEAK/Fn14 interaction induces cell proliferation and inflammatory responses.Serum TWEAK increases in patients with certain subtypes of psoriasis,and varies with some therapies.This review summarizes the role of TWEAK/Fn14 signals in the pathogenesis of psoriasis as well as the potential diagnostic and therapeutic approaches for patients.