Ultraviolet B radiation suppresses endocytosis, subsequent maturation, and migration activity of langerhans cell-like dendritic cells.
Langerhans cells capture exogenous antigens through fluid phase pinocytosis and receptor-mediated endocytosis and migrate to lymph nodes, where they present processed antigen to T cells. Ultraviolet B radiation impairs the antigen-presenting function of Langerhans cells, resulting in antigen-specific immunosuppression of contact hypersensitivity. We tested the notion that ultraviolet B radiation inhibits the endocytic activity of Langerhans cells, leading to impaired migration and maturation. Human monocyte-derived Langerhans cell-like dendritic cells that took up lucifer yellow or fluorescein isothiocyanate dextran exclusively migrated in response to 6Ckine/secondary lymphoid chemokine, and matured, as evidenced by an increase in CD54 and CD86 expression and potent stimulatory activity in allogeneic mixed lymphocyte reaction. Exposing Langerhans cell-like dendritic cells to 20-40 mJ per cm2 of ultraviolet B radiation reduced their endocytic activity in fluid phase pinocytosis (measured by uptake of lucifer yellow) and in receptor-mediated endocytosis (measured by uptake of fluorescein isothiocyanate dextran). Membrane ruffling and CD32 expression were also suppressed by ultraviolet B radiation. Ultraviolet B-irradiated, endocytosing Langerhans cell-like dendritic cells had less movement towards 6Ckine, expressed less CD54 and CD86, and had less effective stimulatory activity in allogeneic mixed lymphocyte reaction than nonirradiated, endocytosing Langerhans cell-like dendritic cells. Endocytosis upregulated tumor necrosis factor alpha production by Langerhans cell-like dendritic cells, but prior ultraviolet B radiation inhibited this enhancement. These data suggested that impaired endocytosis and subsequent inhibitory migration and maturation of Langerhans cells by ultraviolet B radiation could contribute to local immunosuppression of contact hypersensitivity.
Department of Dermatology, Kansai Medical University, Moriguchi, Osaka, Japan.
Kana
K
Mizuno
Hiroyuki
H
Okamoto
Takeshi
T
Horio
D000328:Adult; D002454:Cell Differentiation / Q000528:radiation effects; D002462:Cell Membrane / Q000528:radiation effects; D002465:Cell Movement / Q000528:radiation effects*; D002478:Cells, Cultured; D004705:Endocytosis / Q000528:radiation effects*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D007801:Langerhans Cells / Q000166:cytology* / Q000528:radiation effects*; D010641:Phenotype; D017452:Receptors, IgG / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*
D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10