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8至11周龄的BALB / c小鼠，刮除其背部毛发，形成约2 cm × 3 cm 大小的暴露区域，单笼饲养。随机分为正常对照组( control ，CTRL) 和IMQ 组。在剃毛背部和右耳上接受每日局部剂量的 62.5mg的市售IMQ乳膏（5％)涂抹连续5或6天，即每日用以 3.125mg剂量的活性化合物。经验性地确定了该剂量为在小鼠中 引起最佳和可重复的皮肤炎症的剂量（数据未显示）。类似地用 对照乳膏处理对照组小鼠。 免疫组织化学分析：用带显色剂标记的特异性抗体在组织细胞原 位通过抗原抗体反应和组织化学的呈色反应，对相应的抗原进行 定性、定位和定量的分析。
FIGURE 9. IMQ-induced skin inflammation is dependent on the IL-23/IL-17 axis.
4. Conclusions
• Here we demonstrate that IMQ-treated mouse skin closely resembles human plaque-type psoriasis with respect to erythema, skin thickening, scaling, epidermal alterations (acanthosis, parakeratosis), and neoangiogenesis, as well as with respect to the inflammatory infiltrate consisting of T cells, neutrophils, DC, and pDC. • Mechanistically, T cells are important for full-blown disease development, as reflected by anti-CD3 depletion treatment and the use of immunodeficient mice. Both IL-23 and IL-17 receptor signaling are absolutely critical to development of disease since genetic knockout of both molecules individually leads to a nearly complete blockade of disease, despite daily IMQ application during the entire 6-day experimental period.
3. Results and discussion
FIGURE 8. IMQ-induced skin inflammation is reduced in immunodeficient RAG2-/-common γ-/-common mice.
3. Results and discussion
文献阅读汇报
汇报人：陈楚楚
Imiquimod-Induced Psoriasis-Like Skin Inflammation in Mice Is Mediated via the IL-23/IL-17 Axis
咪喹莫特通过IL-23/IL-17炎症轴来诱导银屑病样 皮炎小鼠
Contents
1. Introduction
3. Results and discussion
FIGURE 6. Topical IMQ increases percentages of splenic Th17 cells.
3. Results and discussion
FIGURE 7. Depletion of CD3 cells attenuates IMQ-induced skin inflammation.
3. Results and discussion
FIGURE 3. IMQ treatment results in accumulation of T cells, neutrophils, and APC, as well as neoangiogenesis.
3. Results and discussion
2. Experimental section 3. Results and discussion 4. Conclusions
1. Introduction
IMQ(咪喹莫特)是Toll样受体(Toll like receptor，TLR) 7/8的激动剂，当局部应用于小鼠时，会诱发和加重一种 慢性炎症性皮肤病—银屑病。最近，我们发现IL-23/IL17炎症轴在银屑病的产生中发挥了至关重要的作用。我们 假设IMQ引起的皮炎小鼠可以作为银屑病样皮炎发病机制 的分析模型并评估了其对IL-23/IL-17炎症轴依赖。我们 对小鼠的背部皮肤日常应用咪喹莫特，引起了小鼠鳞状皮 肤损伤，其类似于斑块型银屑病。这些病变表现为表皮的 增殖，分化的异常，微组织中嗜中性粒细胞的表皮积聚， 新生血管的形成，以及CD4+T细胞、树突状细胞树突状细 胞、浆细胞样树突状细胞的浸润。IMQ诱导IL-23、IL-17A 和IL-17F在表皮中的表达，以及脾脏中Th17细胞的增加。 IMQ引起的皮炎部分依赖于T细胞的存在，IMQ诱导的皮炎 部分依赖于T细胞的存在，而疾病发展几乎在IL-23或IL17受体缺陷的小鼠中完全阻断，表明IL-23/IL-17轴起到 了关键作用。总之，先天的TLR7/8配体咪喹莫特唯一的应 用就是通过IL-23/IL-17炎症轴来快速诱发非常类似于人 牛皮癣的皮炎。这种快速和方便的模型使得银屑病的致病 机制能够进一步阐明以及银屑病的新疗法得以评价。
FIGURE 4. IMQ transiently induces cytokines of the IL-23/IL-17 axis in skin.
பைடு நூலகம்
3. Results and discussion
FIGURE 5. Topical IMQ increases spleen mass and alters its cellular composition.
1. Introduction
本文献的方法： BALB/c 小鼠随机分为正常对照组和咪喹莫特 组，采用PASI 评分观察银屑病样小鼠模型皮 损动态变化; 光镜观察皮损组织形态学变化; 采用流式细胞仪、实时荧光定量PCR 对小鼠 血清及皮肤组织中细胞因子含量和mRNA进行 检测。
2. Experimental section
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3. Results and discussion
FIGURE 1. IMQ-induced skin inflammation in mice phenotypically resembles psoriasis.
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3. Results and discussion
FIGURE 2. IMQ treatment alters keratinocyte proliferation and differentiation.