ArticleThe Journal of clinical investigation2014
Decreased RORC-dependent silencing of prostaglandin receptor EP2 induces autoimmune Th17 cells.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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.
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.
Who cites it
23 citing papers in PubMed, 44 citations in OpenAlex.
- Ketogenic diets attenuate cyclooxygenase and lipoxygenase gene expression in multiple sclerosis.EBioMedicine · 2018Trial
- Potential Roles of Prostaglandins PGD2, PGJ2, and PGE2 in the Pathogenesis of Systemic Lupus Erythematosus.International journal of molecular sciences · 2026Review
- Integrative multi-omics analysis identifies genetically supported druggable targets for inflammatory bowel disease.Journal, genetic engineering & biotechnology · 2025Article
- Heterogeneity of T cells regulates tumor immunity mediated by Helicobacter pylori infection in gastric cancer.BMC cancer · 2025Article
- Exploring Oxylipins in Host-Microbe Interactions and Their Impact on Infection and Immunity.Current issues in molecular biology · 2025Review
- Arachidonic acid-derived lipid mediators in multiple sclerosis pathogenesis: fueling or dampening disease progression?Journal of neuroinflammation · 2024Review
- TH17 cell: a double-edged sword in the development of inflammatory bowel disease.Therapeutic advances in gastroenterology · 2024Review
- Joint together: The etiology and pathogenesis of ankylosing spondylitis.Frontiers in immunology · 2022Review
- Membrane-bound IL-6R is upregulated on Th17 cells and inhibits Treg cell migration by regulating post-translational modification of VASP in autoimmune arthritis.Cellular and molecular life sciences : CMLS · 2021Article
- Prostaglandin EScience advances · 2021Article
- International Union of Basic and Clinical Pharmacology. CIX. Differences and Similarities between Human and Rodent Prostaglandin EPharmacological reviews · 2020Article
- Prostaglandin receptor EP4 expression by Th17 cells is associated with high disease activity in ankylosing spondylitis.Arthritis research & therapy · 2019Article
- T cell-intrinsic prostaglandin EThe Journal of allergy and clinical immunology · 2019Article
- Prostaglandin-cytokine crosstalk in chronic inflammation.British journal of pharmacology · 2019Review
- Activated β-catenin in Foxp3Nature immunology · 2018Article
- Intestinal host defense outcome is dictated by PGEProceedings of the National Academy of Sciences of the United States of America · 2018Article
- mPGES1-Dependent Prostaglandin EJournal of immunology (Baltimore, Md. : 1950) · 2018Article
- mPGES-1-Mediated Production of PGEFrontiers in immunology · 2018Article
- The dichotomous nature of T helper 17 cells.Nature reviews. Immunology · 2017Review
- Phosphoproteomics Reveals Regulatory T Cell-Mediated DEF6 Dephosphorylation That Affects Cytokine Expression in Human Conventional T Cells.Frontiers in immunology · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Prostaglandin E2 (PGE2) promotes Th17 expansion while otherwise inhibiting other CD4+ T cell subsets. Here, we identified a PGE2-dependent pathway that induces pathogenic Th17 cells in autoimmune disease and is regulated by the transcription factor RORC. Compared with other CD4+ cell types from healthy subjects, there is a surprising lack of the prostaglandin receptor EP2 on Th17 cells; therefore, we examined the hypothesis that RORγt, which is highly expressed in Th17 cells, mediates EP2 downregulation. Chromatin immunoprecipitation followed by DNA sequencing revealed that RORγt binds directly to Ptger2 (the gene encoding EP2 receptor) in Th17 cells isolated from WT mice. In Th17 cells isolated from humans, RORC repressed EP2 by directly silencing PTGER2 transcription, and knock down of RORC restored EP2 expression in Th17 cells. Compared with Th17 cells from healthy individuals, Th17 cells from patients with MS exhibited reduced RORC binding to the PTGER2 promoter region, resulting in higher EP2 levels and increased expression of IFN-γ and GM-CSF. Finally, overexpression of EP2 in Th17 cells from healthy individuals induced a specific program of inflammatory gene transcription that produced a pathogenic Th17 cell phenotype. These findings reveal that RORC directly regulates the effects of PGE2 on Th17 cells, and dysfunction of this pathway induces a pathogenic Th17 cell phenotype.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.