Langerhans cells are critical in epicutaneous sensitization with protein antigen via thymic stromal lymphopoietin receptor signaling.
Langerhans cells are critical in epicutaneous sensitization with protein antigen via thymic stromal lymphopoietin receptor signaling.
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DOI：
10.1016/j.jaci.2012.01.063
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发表时间：
2012-04
期刊：
影响因子：
--
通讯作者：
Kabashima K
中科院分区：
文献类型：
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作者：
Nakajima S;Igyártó BZ;Honda T;Egawa G;Otsuka A;Hara-Chikuma M;Watanabe N;Ziegler SF;Tomura M;Inaba K;Miyachi Y;Kaplan DH;Kabashima K
澄清皮肤树突状细胞亚群以及胸腺基质淋巴细胞生成素 (TSLP) 信号在蛋白质抗原的表皮致敏中的作用，如在特应性皮炎的发展中，是一个至关重要的问题。由于 TSLP 在朗格汉斯细胞 (LC) 附近高表达，我们试图阐明我们的假设，即 LC 通过 TSLP 信号传导在蛋白质抗原的表皮致敏中发挥重要作用。通过使用Langerin-白喉毒素受体敲入小鼠和人Langerin-白喉毒素A转基因小鼠，我们制备了LC缺陷的小鼠。我们还通过骨髓嵌合技术使用 TSLP 受体缺陷小鼠制备了 LC 中 TSLP 受体缺陷的小鼠。我们将这些小鼠应用于卵清蛋白 (OVA) 诱导的表皮致敏模型。表皮应用 OVA 后，条件性 LC 耗竭减轻了临床表现的发展以及血清 OVA 特异性 IgE 增加、OVA 特异性 T 细胞增殖和引流淋巴结中 IL-4 mRNA 表达。一致地，即使在稳定状态下，永久性 LC 耗竭也会导致血清 IgE 水平降低，表明 LC 介导 TH2 局部环境。此外，LC 上缺乏 TSLP 受体的小鼠在表皮 OVA 致敏后消除了 OVA 特异性 IgE 水平的诱导。 LC 通过蛋白质抗原启动表皮致敏，并通过 TSLP 信号传导诱导 TH2 型免疫反应。
The clarification of cutaneous dendritic cell subset and the role of thymic stromal lymphopoietin (TSLP) signaling in epicutaneous sensitization with protein antigens, as in the development of atopic dermatitis, is a crucial issue. Because TSLP is highly expressed in the vicinity of Langerhans cells (LCs), we sought to clarify our hypothesis that LCs play an essential role in epicutaneous sensitization with protein antigens through TSLP signaling. By using Langerin-diphtheria toxin receptor knock-in mice and human Langerin-diphtheria toxin A transgenic mice, we prepared mice deficient in LCs. We also prepared mice deficient in TSLP receptors in LCs by using TSLP receptor–deficient mice with bone marrow chimeric technique. We applied these mice to an ovalbumin (OVA)-induced epicutaneous sensitization model. Upon the epicutaneous application of OVA, conditional LC depletion attenuated the development of clinical manifestations as well as serum OVA-specific IgE increase, OVA-specific T-cell proliferation, and IL-4 mRNA expression in the draining lymph nodes. Consistently, even in the steady state, permanent LC depletion resulted in decreased serum IgE levels, suggesting that LCs mediate the TH2 local environment. In addition, mice deficient in TSLP receptors on LCs abrogated the induction of OVA-specific IgE levels upon epicutaneous OVA sensitization. LCs initiate epicutaneous sensitization with protein antigens and induce TH2-type immune responses via TSLP signaling.