Article abstract
Nature Medicine 15, 633 - 640 (2009)
Published online: 24 May 2009 | doi:10.1038/nm.1968
Prostaglandin E2–EP4 signaling promotes immune inflammation through TH1 cell differentiation and TH17 cell expansion
Chengcan Yao1,3,4, Daiji Sakata1,4, Yoshiyasu Esaki1, Youxian Li1, Toshiyuki Matsuoka1, Kenji Kuroiwa2, Yukihiko Sugimoto2,3 & Shuh Narumiya1
Abstract
Two distinct helper T (TH) subsets, TH1 and TH17, mediate tissue damage and inflammation in animal models of various immune diseases such as multiple sclerosis, rheumatoid arthritis, inflammatory bowel diseases and allergic skin disorders. These experimental findings, and the implication of these TH subsets in human diseases, suggest the need for pharmacological measures to manipulate these TH subsets. Here we show that prostaglandin E2 (PGE2) acting on its receptor EP4 on T cells and dendritic cells not only facilitates TH1 cell differentiation but also amplifies interleukin-23–mediated TH17 cell expansion in vitro. Administration of an EP4-selective antagonist in vivo decreases accumulation of both TH1 and TH17 cells in regional lymph nodes and suppresses the disease progression in mice subjected to experimental autoimmune encephalomyelitis or contact hypersensitivity. Thus, PGE2-EP4 signaling promotes immune inflammation through TH1 differentiation and TH17 expansion, and EP4 antagonism may be therapeutically useful for various immune diseases.
- Department of Pharmacology, Faculty of Medicine, Faculty of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
- Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
- Present addresses: Jinan University College of Pharmacy, Guangzhou, China (C.Y.) and Department of Pharmaceutical Biochemistry, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan (Y.S.).
- These authors contributed equally to this work.
Correspondence to: Shuh Narumiya1 e-mail: snaru@mfour.med.kyoto-u.ac.jp
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
RESEARCH
Characterization of uremic toxin transport by organic anion transporters in the kidneyKidney International Original Article
Transplantation of newborn thymus plus hematopoietic stem cells can rescue supralethally irradiated miceBone Marrow Transplantation Original Article
Prostaglandin E 2 ?EP4 signaling initiates skin immune responses by promoting migration and maturation of Langerhans cellsNature Medicine Article (01 Jun 2003)
See all 51 matches for Research
