Facilitation of Th1-mediated immune response by prostaglandin E receptor EP1.
Prostaglandin E2 (PGE2) exerts its actions via four subtypes of the PGE receptor, EP1-4. We show that mice deficient in EP1 exhibited significantly attenuated Th1 response in contact hypersensitivity induced by dinitrofluorobenzene (DNFB). This phenotype was recapitulated in wild-type mice by administration of an EP1-selective antagonist during the sensitization phase, and by adoptive transfer of T cells from sensitized EP1-/- mice. Conversely, an EP1-selective agonist facilitated Th1 differentiation of naive T cells in vitro. Finally, CD11c+ cells containing the inducible form of PGE synthase increased in number in the draining lymph nodes after DNFB application. These results suggest that PGE2 produced by dendritic cells in the lymph nodes acts on EP1 in naive T cells to promote Th1 differentiation.
Nagamachi
Miyako
M
Department of Pharmacology, Faculty of Medicine, Kyoto University, Kyoto 606-8501, Japan.
Sakata
Daiji
D
Kabashima
Kenji
K
Furuyashiki
Tomoyuki
T
Murata
Takahiko
T
Segi-Nishida
Eri
E
Soontrapa
Kitipong
K
Matsuoka
Toshiyuki
T
Miyachi
Yoshiki
Y
Narumiya
Shuh
S
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D002454:Cell Differentiation; D002934:Cinnamates / Q000494:pharmacology; D003713:Dendritic Cells / Q000276:immunology / Q000502:physiology; D015232:Dinoprostone / Q000502:physiology; D008198:Lymph Nodes / Q000276:immunology / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D011453:Prostaglandins / Q000502:physiology; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000276:immunology*; D058306:Receptors, Prostaglandin E, EP1 Subtype; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
D002934:Cinnamates; C411295:ONO 8713; D011453:Prostaglandins; C545636:Ptger1 protein, mouse; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D015232:Dinoprostone