ArticleNature communications2013
Prostaglandin E₂ promotes Th1 differentiation via synergistic amplification of IL-12 signalling by cAMP and PI3-kinase.
Article in Nature communications, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 119 citations in OpenAlex.
- Gut microbiota in chronic inflammation: the interplay with lipid mediators.Gut microbes · 2026Review
- The update of prostaglandin E2 receptor subtype 4 (EP4) in inflammatory diseases.Genes & diseases · 2026Review
- Inducible cAMP Early Repressor Limits Glycolytic Programming in Regulatory T Cells and Supports Control of Inflammatory Colitis.European journal of immunology · 2026Article
- Dual Modulation of Prostaglandin E2 Receptors EP3 and EP4 Protects β-Cell Mass in a Model of Aggressive Autoimmune Inflammation.Diabetes · 2026Article
- Prostaglandin EProceedings of the National Academy of Sciences of the United States of America · 2025Article
- 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 · 2025Article
- A CD4Immunity · 2025Article
- Pathogenesis of chronic enteropathy associated with theWorld journal of gastroenterology · 2024Review
- Prostaglandin ENature communications · 2024Article
- Crosstalk between efferocytic myeloid cells and T-cells and its relevance to atherosclerosis.Frontiers in immunology · 2024Review
- Soluble adenylyl cyclase contributes to imiquimod-mediated inflammation and is a potential therapeutic target in psoriasis.Experimental dermatology · 2023Article
- Article
- Harnessing prostaglandin ETrends in immunology · 2023Review
- Metabolic regulation by prostaglandin EAllergy · 2023Article
- The role of non-steroidal anti-inflammatory drugs as adjuncts to periodontal treatment and in periodontal regeneration.Journal of translational medicine · 2023Review
- Unique characteristics of lung-resident neutrophils are maintained by PGE2/PKA/Tgm2-mediated signaling.Blood · 2022Article
- Pharmacological antagonism of EP2 receptor does not modify basal cardiovascular and respiratory function, blood cell counts, and bone morphology in animal models.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022Article
- Global Trends in Research of Lipid Metabolism in T lymphocytes From 1985 to 2022: A Bibliometric Analysis.Frontiers in immunology · 2022Article
- Inflammasome-independent functions of NAIPs and NLRs in the intestinal epithelium.Biochemical Society transactions · 2021Review
- Targeting metabotropic glutamate receptor 4 for cancer immunotherapy.Science advances · 2021Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T helper 1 (Th1) cells have critical roles in various autoimmune and proinflammatory diseases. cAMP has long been believed to act as a suppressor of IFN-γ production and Th1 cell-mediated immune inflammation. Here we show that cAMP actively promotes Th1 differentiation by inducing gene expression of cytokine receptors involved in this process. PGE2 signalling through EP2/EP4 receptors mobilizes the cAMP-PKA pathway, which induces CREB- and its co-activator CRTC2-mediated transcription of IL-12Rβ2 and IFN-γR1. Meanwhile, cAMP-mediated suppression of T-cell receptor signalling is overcome by simultaneous activation of PI3-kinase through EP2/EP4 and/or CD28. Loss of EP4 in T cells restricts expression of IL-12Rβ2 and IFN-γR1, and attenuates Th1 cell-mediated inflammation in vivo. These findings clarify the molecular mechanisms and pathological contexts of cAMP-mediated Th1 differentiation and have clinical and therapeutic implications for deployment of cAMP modulators as immunoregulatory drugs.
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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.