UV Radiation Induces the Epidermal Recruitment of Dendritic Cells that Compensate for the Depletion of Langerhans Cells in Human Skin

Abstract

UVR causes skin injury and inflammation, resulting in impaired immune function and increased skin cancer risk. Langerhans cells (LCs), the immune sentinels of the epidermis, are depleted for several days following a single UVR exposure and can be reconstituted from circulating monocytes. However, the differentiation pathways leading to the recovery of a normal pool of LCs is still unclear. To study the dynamic changes in human skin with UV injury, we exposed a cohort of 29 healthy human volunteers to a clinically relevant dose of UVR and analyzed sequential epidermal biopsies for changes in leukocyte and dendritic cell (DC) subsets. UV-induced depletion of CD1a high LC was compensated by sequential appearance of various epidermal leukocytes. CD14 + monocytes were recruited as early as D1 post exposure, followed by recruitment of two inflammatory DC subsets that may represent precursors of LCs. These CD1a low CD207-and the heretofore unknown CD1a low CD207 + DCs appeared at day 1 and day 4 post UVR, respectively, and were endowed with T-cell-activating properties similar to those of LCs. We conclude that recruitment of monocytes and inflammatory DCs appear as a physiological response of the epidermis in order to repair UVR-induced LC depletion associated with immune suppression.