St. John's Institute of Dermatology, King's College London, London, UK.
Eur J Immunol. 2013 Dec;43(12):3138-46. doi: 10.1002/eji.201343801. Epub 2013 Nov 20.
Psoriasis is an inflammatory disease of the skin affecting 2-3% of the population, characterized by a thickening of the epidermis and immune infiltrates throughout the dermis and epidermis, causing skin lesions that can seriously affect quality of life. The study of psoriasis has historically been hampered by the lack of good animal models. Various genetically induced models exist, which have provided some information about possible mechanisms of disease, but these models rely mostly on intrinsic imbalances of homeostasis. However, a mouse model of psoriasiform dermatitis caused by the repeated topical application of Aldara™ containing 5% imiquimod was described in 2009. The mechanisms of action of Aldara™ are complex. Imiquimod is an effective ligand for TLR7 (and TLR8 in humans) and also interferes with adenosine receptor signaling. In addition, isostearic acid present in the Aldara™ vehicle has been shown to be biologically active and of importance for activating the inflammasome. Interestingly, the repetitive application of Aldara™ reveals a complex aetiology involving multiple cell types, cytokines, and inflammatory pathways. In this review, we will dissect the findings of the imiquimod model to date and ask how this model can inform us about the immunological aspects of human disease.
银屑病是一种影响 2-3%人群的皮肤炎症性疾病，其特征是表皮增厚和真皮及表皮内免疫浸润，导致皮肤损伤，严重影响生活质量。银屑病的研究一直受到缺乏良好动物模型的阻碍。存在各种遗传诱导的模型，这些模型提供了一些关于疾病可能机制的信息，但这些模型主要依赖于内在的平衡失调。然而，2009 年描述了一种通过重复局部应用含有 5%咪喹莫特的 Aldara™ 引起银屑病样皮炎的小鼠模型。Aldara™ 的作用机制很复杂。咪喹莫特是 TLR7（人类中的 TLR8）的有效配体，也干扰腺苷受体信号。此外，Aldara™ 载体中的异硬脂酸已被证明具有生物活性，并且对激活炎症小体很重要。有趣的是，Aldara™ 的重复应用揭示了一种涉及多种细胞类型、细胞因子和炎症途径的复杂病因。在这篇综述中，我们将剖析迄今为止咪喹莫特模型的研究结果，并探讨该模型如何为我们了解人类疾病的免疫学方面提供信息。
