Langerhans cells mediate the skin-induced tolerance to ovalbumin via Langerin in a murine model.
Langerhans cells mediate the skin-induced tolerance to ovalbumin via Langerin in a murine model.
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在小鼠模型中，朗格汉斯细胞通过 Langerin 介导皮肤诱导的卵清蛋白耐受性
作者：
Luo Yang;Wang Su;Liu Xiaochun;Wen He;Li Wei;Yao Xu
研究背景表皮致敏是特应性疾病过敏原免疫的重要途径；然而，研究还表明，在完整的皮肤上涂抹蛋白质会诱导抗原特异性耐受。朗格汉斯细胞（LCs）在多种炎症性皮肤病和小鼠模型中发挥免疫抑制作用，而LCs在皮肤诱导耐受中的作用尚不完全清楚。方法利用LCs缺陷的Langerin-DTA小鼠建立皮肤诱导卵清蛋白耐受（OVA）模型。通过酶联免疫吸附测定、流式细胞术和免疫荧光分析 Langerin 与 OVA 的结合。引入Langerin缺陷的纯合Langerin-DTR小鼠来评估Langerin在皮肤诱导耐受中的作用。结果将OVA涂抹在完整但未胶带剥离的皮肤上，减弱了随后用OVA皮下免疫诱导的OVA特异性IgE、IgG1和IgG2a的产生，并且在Langerin-DTA小鼠中消除了抑制作用。与胶带剥离的皮肤相反，应用 OVA 后，完整的皮肤诱导引流淋巴结中 LC 产生 IL-10。 Langerin 可以结合 OVA，并且与宽型小鼠相比，纯合性 Langerin-DTR 小鼠在皮肤诱导耐受模型中表现出相似的体液和细胞免疫反应。结论我们的数据表明，LC 在通过 Langerin 诱导的完整皮肤对蛋白抗原的耐受中至关重要，并且 LC 可能通过 Langerin 靶向调节全身和（或）皮肤炎症性疾病中的免疫反应。
BackgroundEpicutaneous 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.MethodsLangerin‐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.ResultsApplication 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.ConclusionOur 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.