Division of Oral Immunology, Department of Oral Biology, Sendai, Japan.
Division of Orthodontics and Dentofacial Orthopedics, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry, Sendai, 980-8575, Japan.
Sci Rep. 2020 Mar 19;10(1):5050. doi: 10.1038/s41598-020-61875-6.
Nickel (Ni) is the most frequent metal allergen and induces Th1-dependent type-IV allergies. In local skin, epidermal Langerhans cells (LCs) and/or dermal dendritic cells (DCs) uptake antigens and migrate to draining lymph nodes (LNs). However, the subsets of antigen-presenting cells that contribute to Ni presentation have not yet been identified. In this study, we analyzed the Ni-binding capabilities of murine DCs using fluorescent metal indicator Newport Green. Elicitation of Ni allergy was assessed after intradermal (i.d.) injection of Ni-treated DCs into ear pinnae of Ni-sensitized mice. The Ni-binding capabilities of MHC class II CD11c migratory DCs were significantly stronger than those of MHC class II CD11c resident DCs and CD11c PDCA1 MHC class II B220 plasmacytoid DCs. Migratory DCs in skin-draining and mandibular LNs showed significantly stronger Ni-binding capabilities than those in mesenteric and medial iliac LNs. An i.d. injection of IL-1β induced the activation of LCs and dermal DCs with strong Ni-binding capabilities. Ni-binding LCs were detected in draining LNs after i.d. challenge with IL-1β and Ni. Moreover, an i.d. injection of Ni-treated DCs purified from skin-draining LNs elicited Ni-allergic inflammation. These results demonstrated that migratory DCs in skin-draining LNs have strong Ni-binding capabilities and elicit Ni allergy.
镍 (Ni) 是最常见的金属过敏原，可诱导 Th1 依赖性 IV 型过敏。在局部皮肤中，表皮朗格汉斯细胞 (LCs) 和/或真皮树突状细胞 (DCs) 摄取抗原并迁移至引流淋巴结 (LNs)。然而，尚未确定参与 Ni 呈递的抗原呈递细胞亚群。在这项研究中，我们使用荧光金属指示剂 NewPort Green 分析了小鼠 DCs 的 Ni 结合能力。在 Ni 致敏小鼠的耳甲皮内 (i.d.) 注射 Ni 处理的 DC 后，评估 Ni 过敏的诱导。MHC II 类 CD11c 迁移性 DC 的 Ni 结合能力明显强于 MHC II 类 CD11c 驻留 DC 和 CD11c PDCA1 MHC II B220 浆细胞样 DC。皮肤引流和下颌淋巴结中的迁移性 DC 的 Ni 结合能力明显强于肠系膜和内侧髂淋巴结中的迁移性 DC。i.d. 注射 IL-1β 可诱导具有强 Ni 结合能力的 LCs 和真皮 DC 的激活。在 i.d. 挑战后，可在引流淋巴结中检测到具有 Ni 结合能力的 LCs IL-1β 和 Ni。此外，从皮肤引流淋巴结中纯化的 i.d. 注射 Ni 处理的 DC 可引发 Ni 过敏炎症。这些结果表明，引流淋巴结中的迁移性 DC 具有较强的 Ni 结合能力，并引发 Ni 过敏。
