Stimulation of Langerhans Cell Migration in Mice by Tumour Necrosis Factor α and Interleukin 1β
Following contact sensitization or other forms of cutaneous trauma epidermal Langerhans cells (LC) are stimulated to migrate from the skin and to travel, via afferent lymphatics, to draining lymph nodes.1 We have demonstrated previously that tumour necrosis factor α (TNF-α), a keratinocyte-derived epidermal cytokine, provides one stimulus for LC migration.2 It has been shown that intradermal injection of mice with homologous recombinant TNF-α induces a rapid reduction in the frequency of epidermal LC local to the site of exposure and results, somewhat later, in the accumulation of dendritic cells (DC) in draining lymph nodes.3,4 Systemic (intraperitoneal) treatment of mice with a neutralizing anti-TNF-α antibody prior to topical sensitization with oxazolone, a potent contact allergen, was found to inhibit almost completely the accumulation of DC in draining nodes normally provoked by exposure to this chemical. Such treatment was found also to suppress the development of contact sensitization.5 In the present investigations we have examined whether another epidermal cytokine interleukin 1β (IL-1β), a product of LC, also plays a role in LC migration. Attention has focused on IL-lβ for three reasons. First, it has been shown that the development of contact hypersensitivity is compromised in 1L-1ß gene deletion transgenics,6 or in mice that have been treated with an anti-IL-1β antibody.7 Second, there is evidence suggesting that IL-1β, a cytokine which is upregulated very rapidly following contact sensitization8, is able to provoke the increased expression of TNF-α by keratinocytes.7 Third, it has been claimed on the basis of experiments performed with human skin explants that IL-1β may affect LC migration in vitro.9 We here describe investigations in which the influence of IL-1β and TNF-α on LC migration and DC accumulation were examined.
KeywordsDrain Lymph Node Contact Hypersensitivity Epidermal Sheet Afferent Lymphatic Dendritic Cell Number
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