Prostaglandin E Receptor Subtypes EP2 and EP4 Promote TH1 Cell Differentiation and TH17 Cell Expansion Through Different Signaling Modules

Daiji Sakata, Chengcan Yao, Yoshiyasu Esaki, Youxian Li, Toshiyuki Matsuoka, Kenji Kuroiwa, Yukihiko Sugimoto, Shuh Narumiya

    Research output: Contribution to journalArticle


    It is well known that prostaglandin (PG) E2 exerts T cell suppression in vitro through elevating cAMP by its receptors, EP2 and EP4. However, such an action is rarely detected in vivo, leaving PGE2-mediated immunosuppression an enigma. Here we show that under strong TCR stimulation, PGE2 facilitates T helper-1 (TH-1) differentiation through activation of phosphatidylinositol-3-kinase (PI3K) by EP2 and EP4. The PGE2-EP4 signaling is also required for IL-23 production by activated dendritic cells (DCs), and the PGE2-EP2/EP4 signaling amplifies IL-23-mediated TH-17 cell expansion. Administration of an EP4-selective antagonist in vivo to mice subjected to experimental allergic encephalomyelitis (EAE) decreases accumulation of both TH-1 and TH-17 cells in regional lymph nodes, and suppresses the disease progression. These results suggest PGE2 promotes immune inflammation through TH-1 differentiation and TH-17 expansion and the EP4 antagonism is therapeutically useful for various immune diseases.

    Original languageEnglish (US)
    Pages (from-to)S244-S248
    JournalInflammation Research
    Issue number2
    StatePublished - Jan 1 2009


    ASJC Scopus subject areas

    • Immunology
    • Pharmacology

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