title: Effects of contact allergens on human Langerhans cells in skin organ culture: migration, modulation of cell surface molecules, and early expression of interleukin-1 beta protein.
abstract: Epidermal Langerhans cells (LC) and cytokines play a critical role in the initiation phase of contact hypersensitivity reactions in the skin. Most of the studies of these aspects have been performed in animal models and relatively little is known about the human system. Short-term human skin organ cultures, in which LC preserved their characteristics and distribution within the epidermis, were used to examine the time course effects of contact allergens on human LC in situ and whether these effects are mediated by cytokines. Epicutaneous application of nontoxic concentrations of contact allergens 2,4-dinitrofluorobenzene, 2,4-dinitrochlorobenzene, and nickel sulphate, but not the irritants sodium dodecylsuphaye and croton oil or the tolerogen 2,4-dichloronitrobenzene, significantly reduced the total number of LC in the epidermis: remaining LC were localized along the epidermal-dermal junction, suggesting a migration of LC within and out of the epidermis. LC that are migrated to the epidermal-dermal junction showed a decreased expression of CD1a+ and MHC-II and an upregulation of ICAM-I. While these effects were observed after 24 hours, the expression of IL-1 beta protein was induced exclusively by LC as early as 4 hours after skin challenge with contact allergens alone. After 24 hours, contact allergens not only increased the expression of IL-1 beta but also induced the expression of IL-1 alpha, TNF-alpha, GM-CSF, and IL-6 proteins mainly by suprabasal keratinocytes. In an attempt to study the possible relation between allergen-induced epidermal cytokines and the migration and phenotypic changes of LC, skin explants were incubated with corresponding human recombinant (hr) cytokines. After 12 hours, hr IL-1 beta, but not other hr cytokines (IL-1 alpha, TNF-alpha, GM-CSF, and IL-6), induced the migration within and out of the epidermis and decreased the expression of CD1a+ and MHC-II on remaining epidermal LC similar to that caused by contact allergens. Pre-incubation of skin explants with neutralizing IL-1 beta antibodies, but not antibodies to IL-1 alpha, TNF-alpha, or GM-CSF, significantly prevented the allergen-induced migration of LC. This study showed that contact allergens preferentially induced the migration of LC within and out of the epidermis and modulated the expression of cell surface molecules on migrated LC as well as induced the early expression of LC-derived IL-1 beta. We also provide evidence that IL-1 beta is critically involved in contact allergen-induced changes on human epidermal LC and suggest that IL-1 beta plays a role in the initiation of contact hypersensitivity in human skin in vivo.
authors.affiliation: Department of Dermatology, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Rambukkana
authors.forename: F H
authors.initials: FH
authors.lastname: Pistoor
authors.forename: J D
authors.initials: JD
authors.lastname: Bos
authors.forename: M L
authors.initials: ML
authors.lastname: Kapsenberg
authors.forename: P K
authors.initials: PK
authors.lastname: Das
mesh_terms: D000485:Allergens / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism* / Q000502:physiology; D007801:Langerhans Cells / Q000187:drug effects* / Q000502:physiology; D009924:Organ Culture Techniques; D012867:Skin / Q000166:cytology / Q000187:drug effects*; D013997:Time Factors
chemical_list: D000485:Allergens; D016207:Cytokines; D007375:Interleukin-1