IL-1β Is Essential for Langerhans Cell Activation and Antigen Delivery to the Lymph Nodes during Contact Sensitization: Evidence for a Dermal Source of IL-1β

IL-1β−/− mice manifest an impaired contact hypersensitivity response to the hapten trinitrochlorobenzene, with the principle defect expressed during the sensitization phase of this response. Following application of hapten to the skin, epidermal Langerhans cells of IL-1β−/− mice failed to demonstrate the classical phenotype of activation. In addition, the delivery of epicutaneously applied fluorescein isothiocyanate to draining lymph nodes was decreased in IL-1β−/− mice. Hapten delivery to draining lymph nodes could be restored by intradermal injection of recombinant IL-1β. Reconstitution of lethally irradiated IL-1β−/− mice by transfer of wild-type bone marrow restored hapten-stimulated IL-1β mRNA expression, demonstrating that IL-1β production was dependent on bone marrow-derived cells. In wild-type skin, IL-1β expression was upregulated in a time- and dose-dependent fashion following hapten application. Interestingly, prominent IL-1β expressing cells were found in the dermis, suggesting that dermal cells may contribute significantly to the contact hypersensitivity response.