ArticleJournal of immunology (Baltimore, Md. : 1950)2012
A2A adenosine receptor signaling in lymphocytes and the central nervous system regulates inflammation during experimental autoimmune encephalomyelitis.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 108 citations in OpenAlex.
- Characterization of human CD39+ Th17 cells with suppressor activity and modulation in inflammatory bowel disease.PloS one · 2014Trial
- From danger to resolution: targeting purinergic signaling in CNS diseases.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
- Adenosine Signaling in Primary and Metastatic Brain Tumors: Immune Suppression, Tumor Progression, and Therapeutic Opportunities.Molecular neurobiology · 2026Review
- Protection From Demyelination by the Novel Adenosine Dual AJournal of cellular and molecular medicine · 2025Article
- Adenosine ACell communication and signaling : CCS · 2025Article
- The Neuroprotective Role of A2A Adenosine Purinoceptor Modulation as a Strategy Against Glioblastoma.Brain sciences · 2024Review
- Adenosine signaling: a potential therapeutic target for psychogenic erectile dysfunction.American journal of translational research · 2024Review
- Roles of Adenosine Receptor (subtypes AMolecular neurobiology · 2023Article
- Is adenosine deaminase (ADA) activity in saliva and serum a more accurate disease detection tool than traditional redox balance parameters in early-lactating dairy cows?Veterinary research communications · 2023Article
- Adenosine APurinergic signalling · 2023Article
- AFrontiers in immunology · 2023Article
- Adenosine AMolecules (Basel, Switzerland) · 2022Article
- Ultrasound Neuromodulation Reduces Demyelination in a Rat Model of Multiple Sclerosis.International journal of molecular sciences · 2022Article
- The Pharmacological Potential of Adenosine AMolecules (Basel, Switzerland) · 2022Review
- A major role for adenosine APurinergic signalling · 2022Article
- Choroid plexus-selective inactivation of adenosine AJournal of neuroinflammation · 2022Article
- Adenosine and Inflammation: Here, There and Everywhere.International journal of molecular sciences · 2021Review
- Adenosine receptor ligation tips the uveitogenic Th1 and Th17 balance towards the latter in experimental autoimmune uveitis-induced mouse.Current research in immunology · 2021Article
- Upregulation of adenosine A2A receptor and downregulation of GLT1 is associated with neuronal cell death in Rasmussen's encephalitis.Brain pathology (Zurich, Switzerland) · 2020Article
- The Purinergic System as a Pharmacological Target for the Treatment of Immune-Mediated Inflammatory Diseases.Pharmacological reviews · 2019Review
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5 authors at 3 institutions in 1 country.
Funding
Abstract
Extracellular adenosine has an important role in regulating the severity of inflammation during an immune response. Although there are four adenosine receptor (AR) subtypes, the A2AAR is both highly expressed on lymphocytes and known as a prime mediator of adenosine's anti-inflammatory effects. To define the importance of A2AAR signaling during neuroinflammatory disease progression, we used the experimental autoimmune encephalomyelitis (EAE) animal model for multiple sclerosis. In EAE induction experiments, A2AAR antagonist treatment protected mice from disease development and its associated CNS lymphocyte infiltration. However, A2AAR(-/-) mice developed a more severe acute EAE phenotype characterized by more proinflammatory lymphocytes and activated microglia/macrophages. Interestingly, very high levels of A2AAR were expressed on the choroid plexus, a well-established CNS lymphocyte entry point. To determine the contribution of A2AAR signaling in lymphocytes and the CNS during EAE, we used bone marrow chimeric mice. Remarkably, A2AAR(-/-) donor hematopoietic cells potentiated severe EAE, whereas lack of A2AAR expression on nonhematopoietic cells protected against disease development. Although no defect in the suppressive ability of A2AAR(-/-) regulatory T cells was observed, A2AAR(-/-) lymphocytes were shown to proliferate more and produced more IFN-γ following stimulation. Despite this more proinflammatory phenotype, A2AAR antagonist treatment still protected against EAE when A2AAR(-/-) lymphocytes were adoptively transferred to T cell-deficient A2AAR(+/+) mice. These results indicate that A2AAR expression on nonimmune cells (likely in the CNS) is required for efficient EAE development, while A2AAR lymphocyte expression is essential for limiting the severity of the inflammatory response.
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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.