Epicutaneous Immunotherapy Results in Rapid Allergen Uptake by Dendritic Cells through Intact Skin and Downregulates the Allergen-Specific Response in Sensitized Mice
Epicutaneous Immunotherapy Results in Rapid Allergen Uptake by Dendritic Cells through Intact Skin and Downregulates the Allergen-Specific Response in Sensitized Mice
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DOI：
10.4049/jimmunol.1003134
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发表时间：
2011-05-15
影响因子：
4.4
通讯作者：
Dupont, Christophe
中科院分区：
文献类型：
--
作者：
Dioszeghy, Vincent;Mondoulet, Lucie;Dupont, Christophe
在具有各种过敏原的动物模型和牛奶过敏儿童中，完整皮肤上的表皮免疫疗法已被证明是一种有效和安全的过敏替代治疗方法。本研究的目的是分析在致敏BALB/c小鼠中，使用表皮递送系统对沉积在完整皮肤上的过敏原进行免疫处理的不同步骤及其免疫后果。正如预期的那样，当应用于完整的皮肤时，OVA既没有通过皮肤的被动通道，也没有可检测到的全身输送。目前的研究表明，在完整的皮肤上长期应用OVA后，OVA被角质层浅层的树突状细胞吸收，并在内化后运输到引流淋巴结，并根据小鼠先前的致敏水平而变化。当OVA与表皮递送系统反复应用时，特异性局部和全身反应下调，与调节性T细胞的诱导相关。除了对存在过敏原的皮肤功能提供新的见解外，这项研究还表明，至少在保持完整的情况下，皮肤可能具有耐受性。中华免疫学杂志，2011,36(6):529 - 537。
Epicutaneous immunotherapy onto intact skin has proved to be an efficient and safe alternative treatment of allergy in an animal model with various allergens and in children for cow's milk allergy. The aim of this study was to analyze the different steps of the immunological handling of the allergen when deposited on intact skin using an epicutaneous delivery system and its immune consequences in sensitized BALB/c mice. As expected, when applied on intact skin, OVA exhibits neither a passive passage through the skin nor any detectable systemic delivery. The current study demonstrates that, after a prolonged application on intact skin, OVA is taken up by dendritic cells in the superficial layers of the stratum corneum and transported, after internalization, to the draining lymph nodes, with variations according to the previous level of sensitization of the mice. When OVA is applied with the epicutaneous delivery system repeatedly, specific local and systemic responses are down-modulated in association with the induction of regulatory T cells. Besides providing new insights into skin function in the presence of allergens, this study indicates that the skin might have a tolerogenic role, at least when kept intact. The Journal of Immunology, 2011, 186: 5629-5637.