PDF(Pubmed)
Abstract：
Allergic contact dermatitis is a prevalent occupational disease with limited therapeutic options. The chemokine CCL22, a ligand of the chemokine receptor CCR4, directs the migration of immune cells. Here, it is shown that genetic deficiency of CCL22 effectively ameliorated allergic reactions in contact hypersensitivity (CHS), a commonly used mouse model of allergic contact dermatitis. For the pharmacological inhibition of CCL22, DNA aptamers specific for murine CCL22 were generated by the systematic evolution of ligands by exponential enrichment (SELEX). Nine CCL22-binding aptamers were initially selected and functionally tested in vitro. The 29-nt DNA aptamer AJ102.29m profoundly inhibited CCL22-dependent T cell migration and did not elicit undesired Toll-like receptor-dependent immune activation. AJ102.29m efficiently ameliorated CHS in vivo after systemic application. Moreover, CHS-associated allergic symptoms were also reduced following topical application of the aptamer on the skin. Microscopic analysis of skin treated with AJ102.29m ex vivo demonstrated that the aptamer could penetrate into the epidermis and dermis. The finding that epicutaneous application of the aptamer AJ102.29m in a cream was as effective in suppressing the allergic reaction as intraperitoneal injection paves the way for therapeutic use of aptamers beyond the current routes of systemic administration.
摘要：
过敏性接触性皮炎是一种常见的职业病，治疗选择有限。趋化因子CCL22,趋化因子受体CCR4的配体,指导免疫细胞的迁移。这里,研究表明，CCL22的遗传缺陷有效改善了接触性超敏反应（CHS）的过敏反应，一种常用的过敏性接触性皮炎小鼠模型。对于CCL22的药理学抑制,通过指数富集(SELEX)通过配体的系统进化产生对鼠CCL22特异性的DNA适体。最初选择9个CCL22结合适体并在体外进行功能测试。29-ntDNA适体AJ102.29m极大地抑制了CCL22依赖性T细胞迁移，并且不会引起不期望的Toll样受体依赖性免疫激活。全身应用后，AJ102.29m有效改善了体内CHS。此外，在皮肤上局部施用适体后,CHS相关的过敏症状也减少。用AJ102.29m离体处理的皮肤的显微镜分析表明,适体可以渗透到表皮和真皮中。发现适体AJ102.29m在乳膏中的表皮应用在抑制过敏反应方面与腹膜内注射一样有效，为超出目前全身给药途径的适体治疗用途铺平了道路。
