Evidence map›Paper›PMID 19273625›Full record

ArticleThe Journal of experimental medicine2009

Prostaglandin E2 regulates Th17 cell differentiation and function through cyclic AMP and EP2/EP4 receptor signaling.

Katia Boniface, Kristian S Bak-Jensen, Ying Li, Wendy M Blumenschein, Mandy J McGeachy, Terrill K McClanahan, Brent S McKenzie, Robert A Kastelein, Daniel J Cua, René de Waal Malefyt

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 242 papers.

0numbers the graph read from it
0cells of the map it votes in
242citing papers in PubMed
15.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

242 citing papers in PubMed, 468 citations in OpenAlex.

  1. Trial
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  8. Dissecting PGENature communications · 2026
    Article
  9. Ablation of prostaglandin ENature biomedical engineering · 2026
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  16. A time-gated PKA-CREB signaling circuit licenses IL-12 responsiveness and Th1 fate in CD4Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  17. Article
  18. Article
  19. Review
  20. Article

182 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Katia BonifaceDepartment of Immunology, Schering-Plough Biopharma, Palo Alto, CA 94304, USA.
Kristian S Bak-Jensen
Ying Li
Wendy M Blumenschein
Mandy J McGeachy
Terrill K McClanahan
Brent S McKenzie
Robert A Kastelein
Daniel J Cua
René de Waal Malefyt

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Prostaglandins, particularly prostaglandin E2 (PGE2), play an important role during inflammation. This is exemplified by the clinical use of cyclooxygenase 2 inhibitors, which interfere with PGE2 synthesis, as effective antiinflammatory drugs. Here, we show that PGE2 directly promotes differentiation and proinflammatory functions of human and murine IL-17-producing T helper (Th17) cells. In human purified naive T cells, PGE2 acts via prostaglandin receptor EP2- and EP4-mediated signaling and cyclic AMP pathways to up-regulate IL-23 and IL-1 receptor expression. Furthermore, PGE2 synergizes with IL-1beta and IL-23 to drive retinoic acid receptor-related orphan receptor (ROR)-gammat, IL-17, IL-17F, CCL20, and CCR6 expression, which is consistent with the reported Th17 phenotype. While enhancing Th17 cytokine expression mainly through EP2, PGE2 differentially regulates interferon (IFN)-gamma production and inhibits production of the antiinflammatory cytokine IL-10 in Th17 cells predominantly through EP4. Furthermore, PGE2 is required for IL-17 production in the presence of antigen-presenting cells. Hence, the combination of inflammatory cytokines and noncytokine immunomodulators, such as PGE2, during differentiation and activation determines the ultimate phenotype of Th17 cells. These findings, together with the altered IL-12/IL-23 balance induced by PGE2 in dendritic cells, further highlight the crucial role of the inflammatory microenvironment in Th17 cell development and regulation.

Indexed as

AnimalsCell DifferentiationCoculture TechniquesCyclic AMPDinoprostoneGene Expression RegulationHumansImmunologic MemoryInterferon-gammaInterleukin-10Interleukin-17Interleukin-1betaInterleukin-23MiceModels, ImmunologicalReceptors, CCR6Cyclic AMPDinoprostoneInterferon-gammaInterleukin-10Interleukin-17Interleukin-1betaInterleukin-23PTGER2 protein, humanPtger2 protein, mousePTGER4 protein, humanPtger4 protein, mouseReceptors, CCR6Receptors, Interleukin-1Receptors, Prostaglandin EReceptors, Prostaglandin E, EP2 SubtypeReceptors, Prostaglandin E, EP4 Subtype

Identifiers

PMID19273625
PMCPMC2699124
OpenAlexW2097404490

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.