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

Abstract

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
Pages (from-to)S244-S248
JournalInflammation Research
Volume58
Issue number2
DOIs
Publication statusPublished - Jan 1 2014
Externally publishedYes

Fingerprint

Receptors, Prostaglandin E, EP2 Subtype
Receptors, Prostaglandin E, EP4 Subtype
Th17 Cells
Dinoprostone
Cell Differentiation
Interleukin-23
Cyclic AMP Receptors
Phosphatidylinositol 3-Kinase
Autoimmune Experimental Encephalomyelitis
Immune System Diseases
Immunosuppression
Dendritic Cells
Disease Progression
Lymph Nodes
Inflammation
T-Lymphocytes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Immunology

Cite this

Prostaglandin E Receptor Subtypes EP2 and EP4 Promote TH1 Cell Differentiation and TH17 Cell Expansion Through Different Signaling Modules. / Sakata, Daiji; Yao, Chengcan; Esaki, Yoshiyasu; Li, Youxian; Matsuoka, Toshiyuki; Kuroiwa, Kenji; Sugimoto, Yukihiko; Narumiya, Shuh.

In: Inflammation Research, Vol. 58, No. 2, 01.01.2014, p. S244-S248.

Research output: Contribution to journalArticle

Sakata, Daiji ; Yao, Chengcan ; Esaki, Yoshiyasu ; Li, Youxian ; Matsuoka, Toshiyuki ; Kuroiwa, Kenji ; Sugimoto, Yukihiko ; Narumiya, Shuh. / Prostaglandin E Receptor Subtypes EP2 and EP4 Promote TH1 Cell Differentiation and TH17 Cell Expansion Through Different Signaling Modules. In: Inflammation Research. 2014 ; Vol. 58, No. 2. pp. S244-S248.
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