Abstract
The migration of epidermal Langerhans cells (LC) to lymph nodes (LN) is critical in the initiation of contact hypersensitivity (CHS) responses. Studies suggest that contact allergen-induced epidermal proinflammatory cytokines, including IL-1 and TNF-alpha, play important roles in promoting LC migration. Contact allergens also induce epidermal anti-inflammatory cytokines such as IL-10. Since IL-10 down-regulates proinflammatory cytokine production and inhibits CHS, we hypothesized that IL-10 might inhibit LC migration. To test this hypothesis, IL-10 knockout (KO) mice were epicutaneously sensitized with the hapten, FITC, and 24 h later hapten-bearing cells in the draining LN were examined. The number of hapten-bearing cells in the LN was significantly greater in IL-10 KO mice than in wild-type mice. The mutant mice also had an exaggerated CHS to FITC. Pretreatment with anti-TNF-alpha Ab or IL-1R antagonist significantly reduced the number of hapten-bearing cells in the LN, suggesting that IL-10 modulation of LC migration involves IL-1 and TNF-alpha. Moreover, IL-10 KO mice demonstrated a greater increase in TNF-alpha, IL-1alpha, and IL-1beta mRNAs in the allergen-exposed epidermis, and keratinocytes derived from the mutant mice were able to produce higher amounts of TNF-alpha and IL-1alpha protein. These data suggest that IL-10 plays an inhibitory role in LC migration and that this effect may occur via the down-regulation of TNF-alpha and IL-1 production.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Count
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Cell Movement / immunology*
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Dermatitis, Contact / genetics
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Dermatitis, Contact / immunology
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Epidermal Cells
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Epidermis / immunology*
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Epidermis / metabolism
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Fluorescein-5-isothiocyanate / administration & dosage
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Fluorescein-5-isothiocyanate / metabolism
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Haptens / administration & dosage
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Haptens / immunology
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Immune Sera / administration & dosage
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Injections, Intraperitoneal
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Interleukin 1 Receptor Antagonist Protein
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Interleukin-1 / antagonists & inhibitors
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Interleukin-1 / biosynthesis
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Interleukin-1 / genetics
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Interleukin-10 / deficiency*
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Interleukin-10 / genetics*
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Interleukin-10 / pharmacology
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Keratinocytes / drug effects
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Keratinocytes / immunology
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Keratinocytes / metabolism
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Langerhans Cells / immunology*
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Langerhans Cells / metabolism
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Lymph Nodes / cytology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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RNA, Messenger / biosynthesis
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Receptors, Interleukin-1 / antagonists & inhibitors
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Receptors, Interleukin-1 / genetics
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Sialoglycoproteins / administration & dosage
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Sialoglycoproteins / genetics
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / biosynthesis
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / immunology
Substances
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Haptens
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Il1rn protein, mouse
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Immune Sera
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Interleukin 1 Receptor Antagonist Protein
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Interleukin-1
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RNA, Messenger
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Receptors, Interleukin-1
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Sialoglycoproteins
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Tumor Necrosis Factor-alpha
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Interleukin-10
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Fluorescein-5-isothiocyanate