Tracking and quantification of dendritic cell migration and antigen trafficking between the skin and lymph nodes.

Tracking and quantification of dendritic cell migration and antigen trafficking between the skin and lymph nodes.
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DOI:
10.1038/srep06030
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发表时间:
2014-08-12
期刊:
影响因子:
4.6
通讯作者:
Kanagawa O
Kanagawa O
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Tomura M;Hata A;Matsuoka S;Shand FH;Nakanishi Y;Ikebuchi R;Ueha S;Tsutsui H;Inaba K;Matsushima K;Miyawaki A;Kabashima K;Watanabe T;Kanagawa O

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皮肤来源的树突状细胞 (DC) 在维持免疫稳态中发挥着至关重要的作用,因为它们在抗原从皮肤运输到引流淋巴结 (dLN) 中发挥着重要作用。为了量化体内皮肤来源的 DC 的时空调节,我们生成了表达光转换荧光蛋白 KikGR 的敲入小鼠。通过将这些小鼠的皮肤或 dLN 暴露在紫光下,我们能够标记和跟踪内源性皮肤来源的 DC 的迁移和周转。 Langerhans细胞和CD103+DC,包括Langerin+CD103+真皮DC(DDC),从皮肤迁移后在dLN中保留4-4.5天,而CD103−DDC仅持续两天。皮肤刺激物(化学应激)的应用导致 CD103−DDC 从皮肤到 dLN 的迁移瞬时增加 10 倍以上。胶带剥离(机械损伤)导致 CD103−DDC 向 dLN 迁移持久增加四倍,并加速这些细胞外源蛋白抗原的运输。这两种压力都会增加 dLN 内 CD103−DDC 的周转率,导致这些细胞在到达后一天内死亡。因此,CD103−DDC 作为抵抗皮肤侵袭的哨兵,通过增加细胞迁移和抗原从皮肤到 dLN 的运输来做出反应。
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.
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