Reactivity of Langerhans cells in human reconstructed epidermis to known allergens and UV radiation

Epidermal Langerhans cells are the outmost guards of our immune defence system. These cells are directly involved in phenomena such as contact hypersensitivity and UV-induced immunosuppression. Some years ago we succeeded in introducing CD34+-derived Langerhans cells into a reconstructed human epidermis. Here we describe their reactivity after topical exposure of the reconstructed epidermis to known allergens, allergen-inducible cytokines, irritants and UV irradiation. Exposure to allergens for 24 h resulted in an activated appearance of the Langerhans cells and in some cases a decrease in their number. Concomitantly, IL-1β and CD86 mRNA over-expressions were detected in the reconstructed epidermis. A topical treatment with TNF-α or IL-1β revealed that both cytokines induced an activated appearance of the Langerhans cells as early as 4 h following application. Irritants had no effect on the integrated Langerhans cells. Exposure of the reconstructed epidermis to Solar Simulated Radiation caused a dramatic decrease in the number of Langerhans cells and a loss of dendricity in the remaining cells 24 h after irradiation. The topical application of a large spectrum UVA/B filter before irradiation prevented these UV-induced alterations. In our hands, this model provides a promising tool to evaluate the sensitization potential of new compounds and to validate the efficacy of sunscreens to prevent UV-induced immunosuppression.