Establishing and maintaining the Langerhans cell network

Langerhans cells (LCs) are the unique antigen-presenting cell of the epidermis. LCs have long been depicted in textbooks as the archetypical dendritic cell that alerts the immune system upon pathogen induced skin barrier breakage, however recent findings argue instead for a more tolerogenic function. While the LCs that populate the epidermis in steady-state arise from progenitors that seed the skin during embryogenesis, it is now apparent that a second pathway generating LCs from a bone marrow derived progenitor is active in inflammatory settings. This review emphasizes the determinants underpinning the establishment of the LC network in steady-state and under inflammatory conditions, as well as the transcriptional machinery governing their differentiation. The dual origin of LCs raises important questions about the functional differences between these subsets in balancing the epidermal immune response between immunity and tolerance.