Blood-derived dermal langerin+ dendritic cells survey the skin in the steady state.
Blood-derived dermal langerin+ dendritic cells survey the skin in the steady state.
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DOI：
10.1084/jem.20071733
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发表时间：
2007-12-24
影响因子：
15.3
通讯作者：
Merad, Miriam
中科院分区：
文献类型：
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作者：
Ginhoux, Florent;Collin, Matthew P;Bogunovic, Milena;Abel, Michal;Leboeuf, Marylene;Helft, Julie;Ochando, Jordi;Kissenpfennig, Adrien;Malissen, Bernard;Grisotto, Marcos;Snoeck, Hans;Randolph, Gwendalyn;Merad, Miriam
Langerin是一种c型凝集素受体，可识别病原体上的糖基化模式。朗格兰用于鉴定人和小鼠表皮朗格汉斯细胞（LCs），以及真皮和皮肤引流淋巴结（dln）中的迁移性LCs。使用允许在体内条件消融langerin+细胞的小鼠模型，连同同源骨髓嵌合体和异种小鼠作为分化LC和血源性树突状细胞（dc）的工具，我们重新研究了langerin+ dc在皮肤dln中的起源。我们的研究结果表明，与目前的观点相反，皮肤DLN中的langerin+CD8−dc并不完全来自迁移性LCs，还包括血源性langerin+ dc，在到达DLN之前通过真皮层。循环langerin+ dc向皮肤的募集依赖于内皮选择素和CCR2，而它们向皮肤dln的募集需要CCR7，并且不依赖于CD62L。我们还发现循环langerin+ dc在稳定状态下巡逻真皮层，并迁移到携带皮肤抗原的皮肤dln。我们建议，这是免疫监测中一个重要的、以前未被认识到的因素，需要在设计新的疫苗策略时加以考虑。
Langerin is a C-type lectin receptor that recognizes glycosylated patterns on pathogens. Langerin is used to identify human and mouse epidermal Langerhans cells (LCs), as well as migratory LCs in the dermis and the skin draining lymph nodes (DLNs). Using a mouse model that allows conditional ablation of langerin+ cells in vivo, together with congenic bone marrow chimeras and parabiotic mice as tools to differentiate LC- and blood-derived dendritic cells (DCs), we have revisited the origin of langerin+ DCs in the skin DLNs. Our results show that in contrast to the current view, langerin+CD8− DCs in the skin DLNs do not derive exclusively from migratory LCs, but also include blood-borne langerin+ DCs that transit through the dermis before reaching the DLN. The recruitment of circulating langerin+ DCs to the skin is dependent on endothelial selectins and CCR2, whereas their recruitment to the skin DLNs requires CCR7 and is independent of CD62L. We also show that circulating langerin+ DCs patrol the dermis in the steady state and migrate to the skin DLNs charged with skin antigens. We propose that this is an important and previously unappreciated element of immunosurveillance that needs to be taken into account in the design of novel vaccine strategies.