Langerhans cells do not migrate to draining lymph nodes

Epidermal Langerhans cells (LCs) represent the "prototype" migratory antigen presenting cells involved in either immune stimulation or peripheral tolerance. We demonstrate that during both steady-state conditions and skin inflammation, LC migration terminates in the dermis, not in the skin-draining lymph nodes (LNs). We identify a separate population of LC-independent CD207+CD326+ LClike cells in the dermis that home at a slow rate to the LNs. These LClike cells are long-lived, radioresistant and embryonic-derived but, unlike LCs, they are gradually replenished by bone-marrow-derived precursors under steady state conditions. Cutaneous tolerance to weak haptens depends on LClike cells, whereas LCs suppress effector CD8+ T cell functions and inflammation locally in the skin. These findings challenge the paradigm that LCs migrate to draining LNs bringing new insights into cutaneous dendritic cell functions and opens novel avenues in the development of treatments to cure inflammatory skin disorders.