Differential regulation of epidermal langerhans cell migration by interleukins (IL)-1alpha and IL-1beta during irritant- and allergen-induced cutaneous immune responses.
Tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, and IL-18 are all known to contribute to the regulation of epidermal Langerhans cells (LC) migration and the subsequent accumulation of dendritic cells (DC) in draining lymph nodes following skin sensitization. However, the cytokine signals that control these responses following skin irritation have yet to be defined. We demonstrate that IL-1alpha, a cytokine associated with skin injury and inflammation, is able to stimulate the activation and migration from the epidermis of LC and their subsequent accumulation in skin-draining lymph nodes. Stimulation of these responses by IL-1alpha required the local availability of TNF-alpha. Using specific neutralizing antibodies, LC migration induced following skin sensitization with oxazolone (Ox) was found to be dependent upon IL-1beta and independent of a requirement for IL-1alpha. However, the converse was true following stimulation of responses with the nonsensitizing skin irritant sodium lauryl sulfate (SLS). Here, the loss of LC from the epidermis and the accumulation of DC in draining lymph nodes required IL-1alpha and not IL-1beta. Despite utilizing different IL-1 isoforms for LC mobilization, the phenotypic characteristics of DC arriving in draining lymph nodes in response to Ox and SLS were similar with respect to the membrane determinants MHC class II, B7-1, B7-2, and intercellular adhesion molecule-1. These data suggest that contact sensitization and skin irritation employ subtly different cytokine networks in the regulation of LC migration, both involving TNF-alpha but demonstrating differential requirements for IL-1 cytokines. The proposal is that different forms of cutaneous trauma may achieve LC migration through distinct molecular mechanisms.
Syngenta Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, SK10 4TJ, United Kingdom. Marie.Cumberbatch@Syngenta.com
Marie
M
Cumberbatch
Rebecca J
RJ
Dearman
Richard W
RW
Groves
Christos
C
Antonopoulos
Ian
I
Kimber
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000485:Allergens / Q000494:pharmacology*; D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D002469:Cell Separation; D003713:Dendritic Cells / Q000187:drug effects; D003877:Dermatitis, Contact / Q000276:immunology*; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects; D005434:Flow Cytometry; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology*; D007509:Irritants / Q000494:pharmacology*; D007801:Langerhans Cells / Q000502:physiology*; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D010081:Oxazolone / Q000494:pharmacology; D010641:Phenotype; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D000485:Allergens; D007375:Interleukin-1; D007509:Irritants; D014409:Tumor Necrosis Factor-alpha; D010081:Oxazolone