Topical Application of siRNA Targeting Cutaneous Dendritic Cells in Allergic Skin Disease
Topical Application of siRNA Targeting Cutaneous Dendritic Cells in Allergic Skin Disease
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DOI：
10.1007/978-1-60761-588-0_24
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发表时间：
2010-01-01
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影响因子：
--
通讯作者：
Hashiguchi, Masaaki
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文献类型：
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作者：
Azuma, Miyuki;Ritprajak, Patcharee;Hashiguchi, Masaaki
RNA干扰是一种很有前途的沉默特定基因的方法，在治疗应用中具有巨大的潜力。然而，治疗应用的主要障碍是双链RNA（dsRNA）的有限稳定性和缺乏可靠的靶细胞递送方法。皮肤似乎是小干扰RNA（siRNA）治疗的有利靶点。树突状细胞（Dendritic cells，DCs）存在于皮肤和粘膜的防御第一线，这些细胞捕获抗原并在诱导免疫和耐受中起着至关重要的作用。共刺激分子CD86在抗原摄取后原位在DC上被诱导，并且表达CD86的DC迁移到局部淋巴结以将抗原呈递给T细胞。局部应用乳膏乳化的CD86 siRNA改善了小鼠接触性超敏反应（CH）和特应性皮炎（AD）样疾病的临床表现。我们的方法可能有利于治疗过敏性皮肤病。
RNA interference is a promising method for silencing specific genes and has great potential for therapeutic applications. However, the major hurdle for therapeutic application is the limited stability of double-strand RNA (dsRNA) and the absence of a reliable delivery method to target cells. Skin appears to be a favorable target for small interfering RNA (siRNA) therapy. Dendritic cells (DCs) exist in the skin and mucosae on the front lines of defense; these cells capture antigens and play a crucial role in inducing immunity and tolerance.In our recent work, we have shown a successful treatment using CD86 si RNA targeting cutaneous DCs. A costimulatory molecule, CD86, is induced on DCs in situ after antigen uptake, and CD86-expressing DCs migrate to the regional lymph nodes to present antigens to T cells. Topical application of cream-emulsified CD86 siRNA ameliorated the clinical manifestations in murine contact hypersensitivity (CH) and atopic dermatitis (AD)-like disease. Our method may be advantageous for the treatment of allergic skin diseases.