Abstract
PGI(2), which exerts its actions via its specific Gs-coupled I prostanoid receptor (IP), is known to be present in the lymph nodes, but its roles in acquired cutaneous immune responses remain unclear. To investigate the role of PGI(2)-IP signaling in cutaneous immune responses, we applied IP-deficient (Ptgir(-/-)) mice to contact hypersensitivity as a model of acquired immune response and found that Ptgir(-/-) mice exhibited a significantly decreased contact hypersensitivity response. Lymph node cells from sensitized Ptgir(-/-) mice exhibited decreased IFN-gamma production and a smaller T-bet(+) subset compared with control mice. PGI synthase and IP expression were detected in dendritic cells and T cells, respectively, by quantitative real-time PCR analysis, suggesting that PGI(2) produced by dendritic cells acts on IP in T cells. In fact, in vitro Th1 differentiation was enhanced by an IP agonist, and this enhancement was nullified by protein kinase A inhibitor. These results suggest that PGI(2)-IP signaling promotes Th1 differentiation through a cAMP-protein kinase A pathway and thereby initiates acquired cutaneous immune responses.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adoptive Transfer
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Animals
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Cell Differentiation / drug effects
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Cell Differentiation / genetics
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Cell Differentiation / immunology*
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Cells, Cultured
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Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
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Cyclic AMP-Dependent Protein Kinases / physiology
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Dermatitis, Allergic Contact / immunology*
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Dermatitis, Allergic Contact / metabolism
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Dermatitis, Allergic Contact / pathology
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Disease Models, Animal
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Epoprostenol / metabolism*
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Female
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Hypersensitivity, Delayed / immunology
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Hypersensitivity, Delayed / metabolism
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Hypersensitivity, Delayed / pathology
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Knockout
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Protein Kinase Inhibitors / pharmacology
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Receptors, Prostaglandin E / agonists
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Receptors, Prostaglandin E / deficiency
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Receptors, Prostaglandin E / genetics
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Receptors, Prostaglandin E / physiology*
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Receptors, Prostaglandin E, EP1 Subtype
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Signal Transduction / drug effects
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Signal Transduction / genetics
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Signal Transduction / immunology*
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T-Lymphocytes, Cytotoxic / immunology
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T-Lymphocytes, Cytotoxic / metabolism
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T-Lymphocytes, Cytotoxic / pathology
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Th1 Cells / immunology*
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Th1 Cells / metabolism*
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Th1 Cells / pathology
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Up-Regulation / drug effects
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Up-Regulation / genetics
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Up-Regulation / immunology
Substances
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Protein Kinase Inhibitors
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Ptger1 protein, mouse
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Receptors, Prostaglandin E
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Receptors, Prostaglandin E, EP1 Subtype
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Epoprostenol
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Cyclic AMP-Dependent Protein Kinases