Monocytes Give Rise To Langerhans Cells That Preferentially Migrate To Lymph Nodes At Steady State

It is still debated whether the homeostatic function of tissue macrophages is dependent on their origin, and evidence suggests this may depend on the tissue of macrophage residence. Here, we answered this question for Langerhans cells (LCs), an embryonic-derived mononuclear phagocyte that has features of both tissue macrophages and dendritic cells. Using time-course analyses, bone marrow chimeras and fate tracing models, we found that the complete elimination of embryonic-derived LCs at steady state results in their repopulation from circulating monocytes. However, monocyte-derived LCs inefficiently replenished the epidermal niche. Instead, these cells preferentially migrated to skin draining lymph nodes. Mechanistically, we show that the superior migratory capability of monocyte-derived LCs is associated with higher expression of CD207/Langerin, a C-type lectin involved in the capture of skin microbes. Our data shows that ontogeny plays a role in the migratory behavior of epidermal LCs. Overall design: Epidermal LCs from a Cd207-DTR BMC were FACs sorted using a gating strategy and origin was determined using index-sorting for monocyte-derived LC (mLC) and embryonic LC (eLC)