1. Department of Dermatology, University of Innsbruck, Innsbruck, Austria
2. ^*Plastic Surgery, University of Innsbruck, Innsbruck, Austria
3. ^†Department of Internal Medicine, University of Innsbruck, Innsbruck, Austria
4. ^‡Pulmonary Center, Boston University, School of Medicine, Boston, Massachusetts, U.S.A.

Correspondence: Dr Patrizia Stoitzner, Department of Dermatology, University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria. Email: patrizia.stoitzner@uibk.ac.at

Received 2 October 2000; Revised 22 December 2000; Accepted 23 January 2001.

Abstract

Migration of cutaneous dendritic cells is essential for the induction of primary immune responses. Chemotaxis plays an important part in guiding migrating cells through the skin. Therefore, we investigated the influence of interleukin-16, a potent chemoattractant, on the migratory properties of cutaneous dendritic cells. Interleukin-16 added to murine and human skin explant cultures, enhanced emigration of Langerhans cells as well as dermal dendritic cells out of the skin. In contrast to tumor necrosis factor-, intradermally injected interleukin-16 did not reduce the density of Langerhans cells suggesting a chemotactic rather than a mechanistic migration-inducing effect of interleukin-16. In support of these findings, the known migration-promoting effect of tumor necrosis factor- in skin explant cultures could be neutralized by anti-interleukin-16 antibody and vice versa, indicating different but cooperative ways of action for both cytokines. In whole skin explant cultures blocking of the interleukin-16 effect was also achieved with a monoclonal antibody against CD4, the receptor for interleukin-16. In contrast, in cultures of murine epidermis alone no blocking by anti-CD4 became obvious and in CD4-deficient mice Langerhans cell migration in response to interleukin-16 was maintained. This suggests that another receptor for interleukin-16 might be operative for Langerhans cells in the mouse epidermis. Finally, we detected interleukin-16-positive cells in the dermis of skin explants, tumor necrosis factor--treated and contact allergen-treated skin. Taken together, it seems likely that locally secreted interleukin-16 might serve to enhance the migration of cutaneous dendritic cells and optimize the response to foreign antigen encountering the skin.