TLRs to cytokines: Mechanistic insights from the imiquimod mouse model of psoriasis
TLRs to cytokines: Mechanistic insights from the imiquimod mouse model of psoriasis
复制标题
DOI：
10.1002/eji.201343801
复制
发表时间：
2013-12-01
影响因子：
5.4
通讯作者：
Nestle, Frank O.
中科院分区：
文献类型：
--
作者：
Flutter, Barry;Nestle, Frank O.
银屑病是一种影响2-3%人口的皮肤炎性疾病，其特征在于表皮增厚和免疫浸润遍及真皮和表皮，引起可严重影响生活质量的皮肤病变。银屑病的研究历来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稳态的内在不平衡。然而，2009年描述了一种由反复局部应用含有5%咪喹莫特的Aldara引起的银屑病样皮炎小鼠模型。Aldara的作用机制很复杂。咪喹莫特是TLR 7（和人类中的TLR 8）的有效配体，并且还干扰腺苷受体信号传导。此外，已证明Aldara溶媒中存在的异硬脂酸具有生物活性，并且对激活炎性小体具有重要意义。有趣的是，Aldara的重复应用揭示了涉及多种细胞类型，细胞因子和炎症途径的复杂病因。在这篇综述中，我们将剖析咪喹莫特模型的研究结果，并询问该模型如何告知我们人类疾病的免疫学方面。
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.