Nikolaus Romani

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

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.

Cytokine Receptors on Epidermal Langerhans Cells

Epidermal Langerhans cells (LC) are considered members of the dendritic cell system which constitutes a distinct lineage of major histocompatibility complex (MHC) class II-expressing leukocytes specialized to initiate primary immune responses.1 Work of recent years has established LC as a beautiful model to study the life history of dendritic cells and has greatly augmented the current concept that immunostimulatory lymphoid dendritic cells originate from immature nonlymphoid precursor cells in peripheral tissues.2 Accordingly immature “tissue dendritic cells,” such as LC in situ, capture and process antigen in the periphery. They then shut off further processing and, while maturation into potent immunostimulatory “lymphoid dendritic cells” takes place, migrate to the draining lymphoid organs where the immunogen has maximal chance to encounter specific T cells.3 Immature “tissue dendritic cells” in other organs such as lung or liver have now been characterized. However, the functional properties of dendritic cells in their different maturational stages and the corresponding cellular and molecular mechanisms have so far been best analyzed with epidermal LC as a model.