Tumour necrosis factor receptor II (p75) signalling is required for the migration of Langerhans' cells.
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-alpha (TNF-alpha) have been suggested to influence LC migration. There are two distinct membrane receptors for TNF-alpha, TNF receptor I (TNF-R1, p55) and TNF receptor II (TNF-R2, p75), thought to be responsible for distinct TNF-alpha 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-alpha antibody were performed. The results revealed that anti-TNF-alpha 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.
Wang
B
B
Division of Dermatology, University of Toronto, Canada.
Kondo
S
S
Shivji
G M
GM
Fujisawa
H
H
Mak
T W
TW
Sauder
D N
DN
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D004817:Epidermis / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D018390:Gene Targeting; D007111:Immunity, Cellular / Q000502:physiology; D007801:Langerhans Cells / Q000502:physiology*; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000502:physiology*; D047889:Receptors, Tumor Necrosis Factor, Type II; D015398:Signal Transduction / Q000502:physiology*
D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II