A Close-Up View of Migrating Langerhans Cells in the Skin

Abstract

Langerhans cells of the epidermis and dermal dendritic cells screen the skin for invading antigens. They initiate primary immune responses after migrating from sites of antigen uptake to lymphoid organs. The skin is a feasible model to study the morphology and regulation of dendritic cell migration. We therefore used murine skin explant cultures for tracking the pathways of dendritic cell migration by electron microscopy. Several novel observations are reported. (i) In 48 h cultures of epidermal sheets numerous Langerhans cells migrated out between keratinocytes extending long and thin cytoplasmic processes ("veils"). (ii) Langerhans cells in transition from epidermis to dermis were observed by transmission electron microscopy. Where Langerhans cells penetrated the basement membrane, the lamina densa was focally absent. (iii) This was highlighted by scanning electron microscopy, which presented the basement membrane as a tightly packed and dense network of fibrils. (iv) Scanning electron microscopy of the dermis revealed dendritic cells extending their cytoplasmic processes and clinging to collagen fibrils. (v) Entry of dendritic cells into dermal lymphatics was observed by transmission electron microscopy. It occurred by transmigration through intercellular spaces of adjacent endothelial cells. Entry through wide gaps between endothelial cells also seemed to take place. (vi) Dendritic cells inside the afferent lymphatics frequently carried material such as melanosomes and apoptotic bodies. These observations visualize the cumbersome pathway that dendritic cells have to take when they generate immunity.