title: Reactivity of Langerhans cells in human reconstructed epidermis to known allergens and UV radiation.
abstract: 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-1beta and CD86 mRNA over-expressions were detected in the reconstructed epidermis. A topical treatment with TNF-alpha or IL-1beta 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.
authors.affiliation: L'OREAL Recherche, Centre Charles Zviak, 90 rue du Général Roguet, 92583 Clichy Cedex, France. vfacy@rd.loreal.com
authors.forename: V
authors.initials: V
authors.lastname: Facy
authors.forename: V
authors.initials: V
authors.lastname: Flouret
authors.forename: M
authors.initials: M
authors.lastname: Régnier
authors.forename: R
authors.initials: R
authors.lastname: Schmidt
mesh_terms: D000485:Allergens / Q000633:toxicity*; D015703:Antigens, CD / Q000096:biosynthesis; D051940:B7-2 Antigen; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects* / Q000528:radiation effects*; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000096:biosynthesis; D015603:Keratinocytes / Q000187:drug effects / Q000528:radiation effects / Q000648:ultrastructure; D007801:Langerhans Cells / Q000187:drug effects* / Q000528:radiation effects* / Q000648:ultrastructure; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013473:Sunscreening Agents / Q000494:pharmacology; D014466:Ultraviolet Rays
chemical_list: D000485:Allergens; D015703:Antigens, CD; D051940:B7-2 Antigen; C497964:CD86 protein, human; D016207:Cytokines; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D013473:Sunscreening Agents