Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China.
Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
Allergy. 2019 Sep;74(9):1738-1747. doi: 10.1111/all.13813. Epub 2019 May 15.
Epicutaneous sensitization is an important route of immunization for allergens in atopic diseases; however, studies have also shown that application with protein on the intact skin induces antigen-specific tolerance. Langerhans cells (LCs) play an immunosuppressive role in several inflammatory skin diseases and mouse models, and the role of LCs in the skin-induced tolerance is not fully understood.
Langerin-DTA mice that were deficient in LCs were utilized to produce the model of skin-induced tolerance to ovalbumin (OVA). Binding of Langerin to OVA was analyzed by enzyme-linked immunosorbent assay, flow cytometry, and immunofluorescence. Homozygous Langerin-DTR mice that were deficient in Langerin were introduced to assess the role of Langerin in the skin-induced tolerance.
Application with OVA onto the intact, but not tape-stripped, skin attenuated the production of OVA-specific IgE, IgG1, and IgG2a induced by subsequent subcutaneous immunization with OVA, and the inhibitory effects were abolished in Langerin-DTA mice. In contrast to the tape-stripped skin, the intact skin induced the production of IL-10 by LCs in draining lymph node after application with OVA. Langerin could bind OVA, and homozygous Langerin-DTR mice demonstrated similar humoral and cellular immune responses in the model of skin-induced tolerance compared to wide-type mice.
Our data suggested that LCs were critical in the intact skin-induced tolerance to protein antigen via Langerin, and LCs might be targeted via Langerin to regulate the immune responses in systemic and (or) skin inflammatory diseases.
经皮致敏是特应性疾病中变应原免疫的重要途径；然而，研究也表明，在完整皮肤上应用蛋白质会诱导抗原特异性耐受。朗格汉斯细胞（LCs）在几种炎症性皮肤病和小鼠模型中发挥免疫抑制作用，LCs 在皮肤诱导耐受中的作用尚未完全阐明。
利用缺乏 LCs 的 Langerin-DTA 小鼠产生卵清蛋白（OVA）皮肤诱导耐受模型。通过酶联免疫吸附试验、流式细胞术和免疫荧光分析 Langerin 与 OVA 的结合。引入缺乏 Langerin 的纯合 Langerin-DTR 小鼠来评估 Langerin 在皮肤诱导耐受中的作用。
将 OVA 应用于完整但未经胶带剥离的皮肤可减弱随后用 OVA 皮下免疫诱导的 OVA 特异性 IgE、IgG1 和 IgG2a 的产生，而在 Langerin-DTA 小鼠中抑制作用被消除。与胶带剥离皮肤相比，完整皮肤在应用 OVA 后诱导引流淋巴结中 LCs 产生 IL-10。Langerin 可以结合 OVA，并且纯合 Langerin-DTR 小鼠在皮肤诱导耐受模型中表现出与野生型小鼠相似的体液和细胞免疫反应。
我们的数据表明，LCs 通过 Langerin 在完整皮肤诱导蛋白抗原耐受中起关键作用，并且可以通过 Langerin 靶向 LCs 来调节全身性和（或）皮肤炎症性疾病中的免疫反应。
