RNA Aptamers Recognizing Murine CCL17 Inhibit T Cell Chemotaxis and Reduce Contact Hypersensitivity In Vivo.
RNA Aptamers Recognizing Murine CCL17 Inhibit T Cell Chemotaxis and Reduce Contact Hypersensitivity In Vivo.
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DOI：
10.1016/j.ymthe.2017.10.005
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发表时间：
2018-01-03
期刊：
影响因子：
--
通讯作者：
Förster I
中科院分区：
文献类型：
--
作者：
Fülle L;Steiner N;Funke M;Gondorf F;Pfeiffer F;Siegl J;Opitz FV;Haßel SK;Erazo AB;Schanz O;Stunden HJ;Blank M;Gröber C;Händler K;Beyer M;Weighardt H;Latz E;Schultze JL;Mayer G;Förster I
趋化因子CCL17主要由免疫系统中的树突状细胞（dc）产生，参与多种炎性疾病的发病机制。作为CCR4的配体，CCL17可诱导趋化并促进T细胞- dc相互作用。我们报道了两种新的RNA适体的鉴定，它们在体外和体内被证实具有中和CCL17的能力。两种适体均以剂量依赖的方式有效抑制CCR4+淋巴瘤株BW5147.3向CCL17的定向迁移。为了研究这些适体在体内的作用，我们使用了小鼠接触性超敏反应模型。系统应用适配体可显著防止接触致敏剂致敏小鼠耳肿胀和T细胞向耳内浸润。这项原理验证研究的结果证实了适体是ccl17介导的趋化性的有效抑制剂。ccl17特异性适配体可能用于治疗或预防人类过敏性和炎症性疾病。趋化因子CCL17促进T细胞吸引外周组织，从而加剧炎症反应。f<s:1> lle等人使用SELEX选择了高亲和力适配体，在小鼠接触性过敏中中和CCL17。由于它们的小尺寸和结构特性，这些适体可能成为治疗过敏性皮肤病的新的多功能药物。
The chemokine CCL17, mainly produced by dendritic cells (DCs) in the immune system, is involved in the pathogenesis of various inflammatory diseases. As a ligand of CCR4, CCL17 induces chemotaxis and facilitates T cell-DC interactions. We report the identification of two novel RNA aptamers, which were validated in vitro and in vivo for their capability to neutralize CCL17. Both aptamers efficiently inhibited the directed migration of the CCR4+ lymphoma line BW5147.3 toward CCL17 in a dose-dependent manner. To study the effect of these aptamers in vivo, we used a murine model of contact hypersensitivity. Systemic application of the aptamers significantly prevented ear swelling and T cell infiltration into the ears of sensitized mice after challenge with the contact sensitizer. The results of this proof-of-principle study establish aptamers as potent inhibitors of CCL17-mediated chemotaxis. Potentially, CCL17-specific aptamers may be used therapeutically in humans to treat or prevent allergic and inflammatory diseases. The chemokine CCL17 promotes T cell attraction to peripheral tissues and thereby exacerbates inflammatory reactions. Using SELEX, Fülle et al. selected high-affinity aptamers, which neutralize CCL17 in murine contact hypersensitivity. Because of their small size and structural properties, such aptamers may represent new versatile drugs for allergic skin diseases.
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DOI：
10.1084/jem.194.6.847
发表时间：
2001-09-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Iellem A;Mariani M;Lang R;Recalde H;Panina-Bordignon P;Sinigaglia F;D'Ambrosio D
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D'Ambrosio D
DOI：
10.4049/jimmunol.1302175
发表时间：
2013-11-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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作者：
Kitajima M;Ziegler SF
通讯作者：
Ziegler SF
影响因子：
158.5
作者：
Gragoudas, ES;Adamis, AP;Guyer, DR
通讯作者：
Guyer, DR
DOI：
10.1007/978-1-4939-3197-2_7
发表时间：
2016-01-01
期刊：
NUCLEIC ACID APTAMERS
影响因子：
--
作者：
Blank, Michael
通讯作者：
Blank, Michael
影响因子：
29.4
作者：
Heiseke, Alexander F.;Faul, Antonia C.;Reindl, Wolfgang
通讯作者：
Reindl, Wolfgang