title: Prostaglandin I2-IP signaling promotes Th1 differentiation in a mouse model of contact hypersensitivity.
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.
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Saeko
authors.initials: S
authors.lastname: Nakajima
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Honda
authors.forename: Daiji
authors.initials: D
authors.lastname: Sakata
authors.forename: Gyohei
authors.initials: G
authors.lastname: Egawa
authors.forename: Hideaki
authors.initials: H
authors.lastname: Tanizaki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Otsuka
authors.forename: Catharina Sagita
authors.initials: CS
authors.lastname: Moniaga
authors.forename: Takeshi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Miyachi
authors.forename: Shuh
authors.initials: S
authors.lastname: Narumiya
authors.forename: Kenji
authors.initials: K
authors.lastname: Kabashima
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D017449:Dermatitis, Allergic Contact / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D011464:Epoprostenol / Q000378:metabolism*; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D018078:Receptors, Prostaglandin E / Q000819:agonists / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D058306:Receptors, Prostaglandin E, EP1 Subtype; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology
chemical_list: D047428:Protein Kinase Inhibitors; C545636:Ptger1 protein, mouse; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D011464:Epoprostenol; D017868:Cyclic AMP-Dependent Protein Kinases