Migration of Langerhans cells and dermal dendritic cells in skin organ cultures: augmentation by TNF-alpha and IL-1 beta

Migration from sites of antigen encounter to lymphoid organs is essential t o the strong immunogenic function of dendritic cells (DC), In the skin, mig ration proceeds through dermal lymphatic vessels and is regulated in an inc ompletely understood way by inflammatory mediators, We studied the effects of tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 bet a) in mouse skin organ cultures by direct enumeration of migrating DC and b y immunohistochemistry. (1) Neutralizing antibodies to TNF-alpha and IL-1 b eta inhibited migration of DC, also in human skin explants (TNF-alpha). (2) TNF-alpha at low concentrations (50 U/mL) anti TL-1 beta (50-3000 U/mL) au gmented migration to about 150% of spontaneous migration (3) High concentra tions of TNF-alpha (5000 U/mL) inhibited migration by approximately 50%. (4 ) DC migration from skin explants of TNF-alpha/lymphotoxin-alpha double-def icient mice and TNF-receptor type 1 and 2 double knock out mice was not imp aired. (5) TNF-alpha effects were neutralized by anti-IL-1 beta, and vice v ersa, We conclude that in normal animals both TNF-alpha and IL-1 beta are r equired for BC migration to occur. In the complete absence of one cytokine (TNF-alpha), however, backup mechanisms step in.