Tomura Michio, Hata Akihiro, Matsuoka Satoshi, Shand Francis H W, Nakanishi Yasutaka, Ikebuchi Ryoyo, Ueha Satoshi, Tsutsui Hidekazu, Inaba Kayo, Matsushima Kouji, Miyawaki Atsushi, Kabashima Kenji, Watanabe Takeshi, Kanagawa Osami
1] Center for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Kyoto 606-8501, Japan [2] Laboratory for Autoimmune Regulation, Research Center for Allergy and Immunology, RIKEN, 1-7-22 Suehiro-cho, Tsurumi, Yokohama City, Kanagawa 230-0045, Japan [3] Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, 7-3- 1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Center for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Kyoto 606-8501, Japan.
Sci Rep. 2014 Aug 12;4:6030. doi: 10.1038/srep06030.
Skin-derived dendritic cells (DCs) play a crucial role in the maintenance of immune homeostasis due to their role in antigen trafficking from the skin to the draining lymph nodes (dLNs). To quantify the spatiotemporal regulation of skin-derived DCs in vivo, we generated knock-in mice expressing the photoconvertible fluorescent protein KikGR. By exposing the skin or dLN of these mice to violet light, we were able to label and track the migration and turnover of endogenous skin-derived DCs. Langerhans cells and CD103(+)DCs, including Langerin(+)CD103(+)dermal DCs (DDCs), remained in the dLN for 4-4.5 days after migration from the skin, while CD103(-)DDCs persisted for only two days. Application of a skin irritant (chemical stress) induced a transient >10-fold increase in CD103(-)DDC migration from the skin to the dLN. Tape stripping (mechanical injury) induced a long-lasting four-fold increase in CD103(-)DDC migration to the dLN and accelerated the trafficking of exogenous protein antigens by these cells. Both stresses increased the turnover of CD103(-)DDCs within the dLN, causing these cells to die within one day of arrival. Therefore, CD103(-)DDCs act as sentinels against skin invasion that respond with increased cellular migration and antigen trafficking from the skin to the dLNs.
皮肤来源的树突状细胞（DCs）在维持免疫稳态中发挥着关键作用，因为它们在将抗原从皮肤运输到引流淋巴结（dLNs）中起作用。为了量化体内皮肤来源的DCs的时空调节，我们构建了表达光转化荧光蛋白KikGR的敲入小鼠。通过将这些小鼠的皮肤或dLN暴露于紫光下，我们能够标记并追踪内源性皮肤来源的DCs的迁移和更新。朗格汉斯细胞和CD103(+)DCs，包括Langerin(+)CD103(+)真皮DCs（DDCs），从皮肤迁移后在dLN中停留4-4.5天，而CD103(-)DDCs仅持续两天。应用皮肤刺激物（化学应激）导致CD103(-)DDCs从皮肤向dLN的迁移瞬时增加超过10倍。胶带剥离（机械损伤）导致CD103(-)DDCs向dLN的迁移持久增加四倍，并加速这些细胞对外源蛋白抗原的运输。两种应激都增加了dLN内CD103(-)DDCs的更新，导致这些细胞在到达后一天内死亡。因此，CD103(-)DDCs作为抵御皮肤入侵的哨兵，通过增加细胞迁移和从皮肤到dLNs的抗原运输做出反应。
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