Migration of Langerhans cells and dermal dendritic cells in skin organ cultures: augmentation by TNF‐α and IL‐1 β

Migration from sites of antigen encounter to lymphoid organs is essential to the strong immunogenic function of dendritic cells (DC). In the skin, migration proceeds through dermal lymphatic vessels and is regulated in an incompletely understood way by inflammatory mediators. We studied the effects of tumor necrosis factor α (TNF‐α) and interleukin‐1β (IL‐1β) in mouse skin organ cultures by direct enumeration of migrating DC and by immunohistochemistry. (1) Neutralizing antibodies to TNF‐α and IL‐1β inhibited migration of DC, also in human skin explants (TNF‐α). (2) TNF‐α at low concentrations (50 U/mL) and IL‐1β (50–3000 U/mL) augmented migration to about 150% of spontaneous migration. (3) High concentrations of TNF‐α (5000 U/mL) inhibited migration by approximately 50%. (4) DC migration from skin explants of TNF‐α/lymphotoxin‐α double‐deficient mice and TNF‐receptor type 1 and 2 double knock‐out mice was not impaired. (5) TNF‐α effects were neutralized by anti‐IL‐1β, and vice versa. We conclude that in normal animals both TNF‐α and IL‐1 β are required for DC migration to occur. In the complete absence of one cytokine (TNF‐α), however, backup mechanisms step in. J. Leukoc. Biol. 66: 462–470; 1999.