ArticleFrontiers in pharmacology2021
Upregulation of Phosphodiesterase 2A Augments T Cell Activation by Changing cGMP/cAMP Cross-Talk.
Article in Frontiers in pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
15 citing papers in PubMed, 18 citations in OpenAlex.
- Mitochondrial Abundant Heat Soluble (MAHS) Protein Expression Modulates Metabolic Dynamics in Human Adipose-Derived Stem Cells.International journal of molecular sciences · 2026Article
- Spatial and Single-Cell Transcriptomics Reveal Keratinocytes as Key Players in Vulvar Lichen Sclerosus Pathogenesis.The Journal of investigative dermatology · 2026Article
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Potential molecular metabolic mechanisms underlying the effects of cimifugin in gastric cancer through single-cell and bulk RNA sequencing combined with network pharmacology.Journal of gastrointestinal oncology · 2024Article
- Dynamics of Changes in the cAMP/cGMP Concentration Ratio in the Thymus and Spleen of Laboratory Mice during Vaccination against Plague and Tularemia against the Background of Immunomodulation.Bulletin of experimental biology and medicine · 2024Article
- cAMP-PKA/EPAC signaling and cancer: the interplay in tumor microenvironment.Journal of hematology & oncology · 2024Review
- Proteomics analysis of periplaque and chronic inactive multiple sclerosis lesions.Frontiers in molecular neuroscience · 2024Article
- Comprehensive analysis of PDE2A: a novel biomarker for prognostic value and immunotherapeutic potential in human cancers.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2024Article
- A mini-review: phosphodiesterases in charge to balance intracellular cAMP during T-cell activation.Frontiers in immunology · 2024Review
- CXCL12 targets the primary cilium cAMP/cGMP ratio to regulate cell polarity during migration.Nature communications · 2023Article
- Article
- Immunomodulatory Effects of Chicken Broth and Histidine Dipeptides on the Cyclophosphamide-Induced Immunosuppression Mouse Model.Nutrients · 2022Article
- Phosphodiesterase 5 inhibitor sildenafil potentiates the antitumor activity of cisplatin by ROS-mediated apoptosis: a role of deregulated glucose metabolism.Apoptosis : an international journal on programmed cell death · 2022Article
- Review
- Regulatory T Cell-Related Gene Indicators in Pulmonary Hypertension.Frontiers in pharmacology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
3',5'-cyclic adenosine monophosphate (cAMP) is well-known for its diverse immunomodulatory properties, primarily inhibitory effects during T cell activation, proliferation, and production of pro-inflammatory cytokines. A decrease in cAMP levels, due to the hydrolyzing activity of phosphodiesterases (PDE), is favoring inflammatory responses. This can be prevented by selective PDE inhibitors, which makes PDEs important therapeutic targets for autoimmune disorders. In this study, we investigated the specific roles of PDE2A and PDE3B in the regulation of intracellular cAMP levels in different mouse T cell subsets. Unexpectedly, T cell receptor (TCR) activation led to a selective upregulation of PDE2A at the protein level in conventional T cells (Tcon), whereas no changes were detected in regulatory T cells (Treg). In contrast, protein expression of PDE3B was significantly higher in both non-activated and activated Tcon subsets as compared to Treg, with no changes upon TCR engagement. Live-cell imaging of T cells expressing a highly sensitive Förster resonance energy transfer (FRET)-based biosensor, Epac1-camps, has enabled cAMP measurements in real time and revealed stronger responses to the PDE2A inhibitors in activated vs non-activated Tcon. Importantly, stimulation of intracellular cGMP levels with natriuretic peptides led to an increase of cAMP in non-activated and a decrease of cAMP in activated Tcon, suggesting that TCR activation changes the PDE3B-dependent positive to PDE2A-dependent negative cGMP/cAMP cross-talk. Functionally, this switch induced higher expression of early activation markers CD25 and CD69. This constitutes a potentially interesting feed-forward mechanism during autoimmune and inflammatory responses that may be exploited therapeutically.
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.