CCR4 Is Critically Involved in Skin Allergic Inflammation of BALB/c Mice
CCR4 Is Critically Involved in Skin Allergic Inflammation of BALB/c Mice
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DOI：
10.1016/j.jid.2018.02.027
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发表时间：
2018-08-01
影响因子：
6.5
通讯作者：
Nakayama, Takashi
中科院分区：
文献类型：
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作者：
Matsuo, Kazuhiko;Nagakubo, Daisuke;Nakayama, Takashi
特应性皮炎是一种慢性炎症性皮肤病，涉及T辅助细胞（Th）2细胞，嗜酸性粒细胞和肥大细胞。尽管CCR 4是Th 2细胞上表达的主要趋化因子受体，并被认为是过敏性疾病的潜在治疗靶点，但其在特应性皮炎中的作用仍不清楚。在这里，通过使用水凝胶贴片作为卵清蛋白的经皮递送装置，（一种抗原）和金黄色葡萄球菌δ毒素（一种肥大细胞激活剂），我们在BALB/c小鼠中有效地诱导急性特应性皮炎样皮肤损伤，BALB/c小鼠是一种倾向于Th 2应答的品系，其特征在于皮肤损伤中嗜酸性粒细胞、肥大细胞和CCR 4表达Th 2细胞的数量增加;血清中总IgE和卵清蛋白特异性IgE水平升高;以及皮肤病变中IL-4、IL-17 A、IL-22、CCL 17、CCL 22和CCR 4表达增加。值得注意的是，相同的模型在C57 BL/6小鼠中效率较低，这是一种倾向于Th 1应答的品系。在BALB/c小鼠中使用这种特应性皮炎模型，我们证明了CCR 4缺乏或CCR 4拮抗剂改善了过敏反应。总之，这些结果表明，CCR 4通过募集表达CCR 4的Th 2细胞和Th 17细胞在BALB/c小鼠的皮肤过敏性炎症中起关键作用。
Atopic dermatitis is a chronic inflammatory skin disease involving T-helper (Th) 2 cells, eosinophils, and mast cells. Although CCR4 is a major chemokine receptor expressed on Th2 cells and regarded as a potential therapeutic target for allergic diseases, its role in atopic dermatitis remains unclear. Here, by using a hydrogel patch as a transcutaneous delivery device for ovalbumin (an antigen) and Staphylococcus aureus delta-toxin (a mast cell activator), we efficiently induced acute atopic dermatitis-like skin lesions in BALB/c mice, a strain prone to Th2 responses, which were characterized by increased numbers of eosinophils, mast cells, and CCR4-expressing Th2 cells in the skin lesions; elevated levels of total and ovalbumin-specific IgE in the sera; and increased expression of IL-4, IL-17A, IL-22, CCL17, CCL22, and CCR4 in the skin lesions. Of note, the same model was less efficient in C57BL/6 mice, a strain prone to Th1 responses. Using this atopic dermatitis model in BALB/c mice, we demonstrated that CCR4-deficiency or a CCR4 antagonist ameliorated the allergic responses. Collectively, these results demonstrate that CCR4 plays a pivotal role in skin allergic inflammation of BALB/c mice by recruiting CCR4-expressing Th2 cells and Th17 cells.