Blood-derived dermal langerin⁺ dendritic cells survey the skin in the steady state

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.