Imiquimod-Induced Psoriasis-Like Skin Inflammation in Mice Is Mediated via the IL-23/IL-17 Axis
Imiquimod-Induced Psoriasis-Like Skin Inflammation in Mice Is Mediated via the IL-23/IL-17 Axis
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DOI：
10.4049/jimmunol.0802999
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发表时间：
2009-05-01
影响因子：
4.4
通讯作者：
Lubberts, Erik
中科院分区：
文献类型：
--
作者：
van der Fits, Leslie;Mourits, Sabine;Lubberts, Erik
局部应用咪喹莫特（IMQ），一种TLR 7/8配体和有效的免疫激活剂，可以诱导和加重银屑病，一种慢性炎症性皮肤病。最近，提出了IL-23/IL-17轴在银屑病中的关键作用。我们假设IMQ诱导的小鼠皮炎可以作为分析银屑病样皮炎致病机制的模型，并评估其IL-23/IL-17轴依赖性。在小鼠背部皮肤上每日施用IMQ诱导类似斑块型银屑病的发炎鳞状皮肤病变。这些病变表现为表皮增殖增加、分化异常、微脓肿中中性粒细胞表皮积聚、新生血管生成和由CD 4（+）T细胞、CD 11 c（+）树突状细胞和浆细胞样树突状细胞组成的浸润。IMQ诱导IL-23、IL-17 A和IL-17 F的表皮表达，以及脾Th 17细胞的增加。IMQ诱导的皮炎部分依赖于T细胞的存在，而疾病的发展几乎完全阻断在小鼠缺乏IL-23或11，47受体，证明了IL-23/IL-17轴的关键作用。总之，先天性TLR 7/8配体IMQ的单独应用迅速诱导皮炎，其非常类似于人银屑病，严重依赖于IL-23/IL-17轴。这种快速方便的模型可以进一步阐明银屑病的致病机制和评价新的治疗方法。免疫学杂志，2009，182：5836-5845.
Topical application of imiquimod (IMQ), a TLR7/8 ligand and potent immune activator, can induce and exacerbate psoriasis, a chronic inflammatory skin disorder. Recently, a crucial role was proposed for the IL-23/IL-17 axis in psoriasis. We hypothesized that IMQ-induced dermatitis in mice can serve as a model for the analysis of pathogenic mechanisms in psoriasis-like dermatitis and assessed its IL-23/IL-17 axis dependency. Daily application of IMQ on mouse back skin induced inflamed scaly skin lesions resembling plaque type psoriasis. These lesions showed increased epidermal proliferation, abnormal differentiation, epidermal accumulation of neutrophils in microabcesses, neoangiogenesis, and infiltrates consisting of CD4(+) T cells, CD11c(+) dendritic cells, and plasmacytoid dendritic cells. IMQ induced epidermal expression of IL-23, IL-17A, and IL-17F, as well as an increase in splenic Th17 cells. IMQ-induced dermatitis was partially dependent on the presence of T cells, whereas disease development was almost completely blocked in mice deficient for IL-23 or the 11,47 receptor, demonstrating a pivotal role of the IL-23/IL-17 axis. In conclusion, the sole application of the innate TLR7/8 ligand IMQ rapidly induces a dermatitis closely resembling human psoriasis, critically dependent on the IL-23/IL-17 axis. This rapid and convenient model allows further elucidation of pathogenic mechanisms and evaluation of new therapies in psoriasis. The Journal of Immunology, 2009, 182: 5836-5845.