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

• Published in: Inflammation research Vol. 58; no. Suppl 2; pp. S244 - S248
• Main Authors: Sakata, Daiji, Yao, Chengcan, Esaki, Yoshiyasu, Li, Youxian, Matsuoka, Toshiyuki, Kuroiwa, Kenji, Sugimoto, Yukihiko, Narumiya, Shuh
• Format: Journal Article
• Language: English
• Published: Basel Birkhäuser-Verlag 01.07.2009
• Subjects: Allergology; Biomedical and Life Sciences; Biomedicine; Dermatology; Immunology; Mini-papers for Young Investigator’s Award Contestants’ Session (Van Arman Award); Neurology; Pharmacology/Toxicology; Rheumatology; Experimental Allergic Encephalomyelitis; PGE2; Immune Inflammation; Wortmannin; Myelin Oligodendrocyte Glycoprotein
• ISSN: 1023-3830; 1420-908X
• DOI: 10.1007/BF03354229

It is well known that prostaglandin (PG) E 2 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 PGE 2 -mediated immunosuppression an enigma. Here we show that under strong TCR stimulation, PGE 2 facilitates T helper-1 (T H -1) differentiation through activation of phosphatidylinositol-3-kinase (PI3K) by EP2 and EP4. The PGE 2 -EP4 signaling is also required for IL-23 production by activated dendritic cells (DCs), and the PGE2-EP2/EP4 signaling amplifies IL-23-mediated T H -17 cell expansion. Administration of an EP4-selective antagonist in vivo to mice subjected to experimental allergic encephalomyelitis (EAE) decreases accumulation of both T H -1 and T H -17 cells in regional lymph nodes, and suppresses the disease progression. These results suggest PGE 2 promotes immune inflammation through T H -1 differentiation and T H -17 expansion and the EP4 antagonism is therapeutically useful for various immune diseases.