Distinct Roles of IL-23 and IL-17 in the Development of Psoriasis-Like Lesions in a Mouse Model
Distinct Roles of IL-23 and IL-17 in the Development of Psoriasis-Like Lesions in a Mouse Model
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DOI：
10.4049/jimmunol.1000148
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发表时间：
2011-04-01
影响因子：
4.4
通讯作者：
Sano, Shigetoshi
中科院分区：
文献类型：
--
作者：
Nakajima, Kimiko;Kanda, Takashi;Sano, Shigetoshi
牛皮癣是一种免疫系统和皮肤之间动态相互作用的炎症性疾病。 IL-23/Th17轴在银屑病的发病机制中发挥着重要作用，尽管IL-23和IL-17在体内的确切贡献仍不清楚。 K5。 Stat3C 转基因小鼠在角质形成细胞内组成型表达激活的 Stat3，这些动物出现的皮肤病变的组织学和细胞因子谱与人类斑块型银屑病相似。在这项研究中，我们表征了抗小鼠 IL-17A、抗小鼠 IL-12/23p40 和抗小鼠 IL-23p19 Abs 对 K5 银屑病样病变发展的影响。 Stat3C 转基因小鼠。用抗IL-12/23p40或抗IL-23p19抗体治疗极大地抑制了K5耳朵中12-O-十四烷酰佛波醇-13-乙酸酯诱导的表皮增生。 Stat3C 小鼠，而抗 IL-17A Ab 的抑制作用相对不太显着。使用抗IL-12/23p40或抗IL-23p19抗体治疗可显着降低皮肤病变中Th17细胞因子（例如IL-17和IL-22）、β-防御素和S100A家族成员的转录水平。然而，抗IL-17A Ab治疗并不影响Th17细胞因子的mRNA水平。将 IL-17A 缺陷型小鼠与 K5 杂交。 Stat3C 小鼠导致 12-O-十四烷酰佛波醇-13-乙酸酯诱导的损伤部分减弱，抗 IL-12/23p40 Ab 治疗进一步减弱这种损伤。对皮内注射 IL-23 的小鼠皮肤引流淋巴结细胞进行 FACS 分析，结果显示产生 IL-22 的 T 细胞和 NK-22 细胞均有所增加。总而言之，该系统提供了一个有用的牛皮癣小鼠模型，并展示了 IL-23 和 IL-17 的不同作用。免疫学杂志，2011，186：4481-4489。
Psoriasis is an inflammatory disease with dynamic interactions between the immune system and the skin. The IL-23/Th17 axis plays an important role in the pathogenesis of psoriasis, although the exact contributions of IL-23 and IL-17 in vivo remain unclear. K5. Stat3C transgenic mice constitutively express activated Stat3 within keratinocytes, and these animals develop skin lesions with histological and cytokine profiles similar to those of human plaque psoriasis. In this study, we characterized the effects of anti-mouse IL-17A, anti-mouse IL-12/23p40, and anti-mouse IL-23p19 Abs on the development of psoriasis-like lesions in K5. Stat3C transgenic mice. Treatment with anti-IL-12/23p40 or anti-IL-23p19 Abs greatly inhibited 12-O-tetradecanoylphorbol-13-acetate-induced epidermal hyperplasia in the ears of K5. Stat3C mice, whereas the inhibitory effect of an anti-IL-17A Ab was relatively less prominent. Treatment with anti-IL-12/23p40 or anti-IL-23p19 Abs markedly lowered transcript levels of Th17 cytokines (e. g., IL-17 and IL-22), beta-defensins, and S100A family members in skin lesions. However, anti-IL-17A Ab treatment did not affect mRNA levels of Th17 cytokines. Crossing IL-17A-deficient mice with K5. Stat3C mice resulted in partial attenuation of 12-O-tetradecanoylphorbol-13-acetate-induced lesions, which were further attenuated by anti-IL-12/23p40 Ab treatment. FACS analysis of skin-draining lymph node cells from mice that were intradermally injected with IL-23 revealed an increase in both IL-22-producing T cells and NK-22 cells. Taken together, this system provides a useful mouse model for psoriasis and demonstrates distinct roles for IL-23 and IL-17. The Journal of Immunology, 2011, 186: 4481-4489.