Tumour necrosis factor receptor II (p75) signalling is required for the migration of Langerhans' cells

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Abstract
Langerhans' cells (LC) represent the major antigen-presenting cells within the epidermis. Following exposure of the skin to antigen, LC take up antigen, migrate into draining lymph nodes (DLN) and present processed antigen to T lymphocytes, thereby initiating an immune response. The molecular mechanisms responsible for LC migration remain unclear. Cytokines, in particular tumour necrosis factor-α (TNF-α) have been suggested to influence LC migration. There are two distinct membrane receptors for TNF-α, TNF receptor I (TNF-R1, p55) and TNF receptor II (TNF-R2, p75), thought to be responsible for distinct TNF-α activities. It is believed that most of TNF biological activities are mediated via TNF-R1. In order to examine the role of TNF-R1 signalling in LC migration, we utilized TNF-R1 gene-targeted mutant mice. Following application of the hapten fluorescein isothiocyanate (FITC), FITC-bearing cells in DLN were examined by flow cytometry. A normal number of FITC+/Ia+ cells (LC) were found in DLN from TNF-R1-deficiency mice, suggesting that TNF-R1-dependent signalling is not crucial for LC migration. To investigate the possibility of signalling through TNF-R2, blocking studies using a neutralizing anti-TNF-α antibody were performed. The results revealed that anti-TNF-α antibody significantly inhibited LC accumulation in DLN in TNF-R1-deficient mice, thus suggesting that TNF-R2 signalling is involved in LC migration from skin to DLN and that murine LC express TNF-R2.

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