Published online
doi:10.1084/jem.20070773
The Journal of Experimental Medicine, Vol. 204, No. 12, 2865-2874
The Rockefeller University Press, 0022-1007 $30.00
© Nagamachi et al.
Facilitation of Th1-mediated immune response by prostaglandin E receptor EP1
Miyako Nagamachi1,2,
Daiji Sakata1,
Kenji Kabashima1,2,
Tomoyuki Furuyashiki1,
Takahiko Murata1,
Eri Segi-Nishida1,
Kitipong Soontrapa1,
Toshiyuki Matsuoka1,
Yoshiki Miyachi2, and
Shuh Narumiya1
1 Department of Pharmacology and 2 Department of Dermatology, Faculty of Medicine, Kyoto University, Kyoto 606-8501, Japan
CORRESPONDENCE Shuh Narumiya: snaru{at}mfour.med.kyoto-u.ac.jp
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.
Abbreviations used: CHS, contact hypersensitivity; COX, cyclooxygenase; cPGES, cytosolic PGE synthase; DNBS, dinitrobenzene sulfonic acid; DNFB, dinitrofluorobenzene; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; LC, Langerhans cell; mPGES-1, membrane-associated PGE synthase-1; PG, prostaglandin; PGES, PGE synthase; T-bet, T-box-expressed-in-T cells.
M. Nagamachi, D. Sakata, and K. Kabashima contributed equally to this work.

CiteULike
Complore
Connotea
Del.icio.us
Digg
Facebook
Reddit
Technorati
Twitter What's this?
This article has been cited by other articles:
-
Chizzolini, C., Chicheportiche, R., Alvarez, M., de Rham, C., Roux-Lombard, P., Ferrari-Lacraz, S., Dayer, J.-M.
(2008). Prostaglandin E2 synergistically with interleukin-23 favors human Th17 expansion. Blood
112: 3696-3703
[Abstract]
[Full Text]