ArticleAmerican journal of translational research2016
Adenosine promotes Foxp3 expression in Treg cells in sepsis model by activating JNK/AP-1 pathway.
Article in American journal of translational research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 54 citations in OpenAlex.
- Review
- The Role of AP-1 in Cancer: Regulation, Tumor Microenvironment and Therapeutic Targeting.Biomolecules · 2026Review
- Cascade-Targeted Nanoparticles for Enhanced Gemcitabine Delivery and Adenosine Metabolism Modulation to Overcome Treatment Resistance in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Purin Metabolism Is Crucial for Regulatory T Cell Stability and Function.European journal of immunology · 2025Review
- High Fat Low Carbohydrate Diet Is Linked to CNS Autoimmunity Protection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The homeostasis and heterogeneity of regulatory T cells in sepsis.Burns & trauma · 2025Article
- Inosine induces stemness features in CAR-T cells and enhances potency.Cancer cell · 2024Article
- Caffeine-folic acid-loaded-chitosan nanoparticles combined with methotrexate as a novel HepG2 immunotherapy targeting adenosine A2A receptor downstream cascade.BMC complementary medicine and therapies · 2023Article
- Review
- NK cells direct the perspective approaches to cancer immunotherapy.Medical oncology (Northwood, London, England) · 2023Review
- Dihydroartemisinin imposes positive and negative regulation on Treg and plasma cells via direct interaction and activation of c-Fos.Communications biology · 2023Article
- T cell-intrinsic STING signaling promotes regulatory T cell induction and immunosuppression by upregulating FOXP3 transcription in cervical cancer.Journal for immunotherapy of cancer · 2022Article
- Dihydroartemisinin beneficially regulates splenic immune cell heterogeneity through the SOD3-JNK-AP-1 axis.Science China. Life sciences · 2022Article
- [Blocking Adenosine/A2AR Pathway for Cancer Therapy].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2022Review
- Exogenous adenosine activates A2A adenosine receptor to inhibit RANKL-induced osteoclastogenesis via AP-1 pathway to facilitate bone repair.Molecular biology reports · 2022Article
- Manipulation of metabolic pathways to promote stem-like and memory T cell phenotypes for immunotherapy.Frontiers in immunology · 2022Review
- CD4Theranostics · 2022Article
- Insulin-binding protein-5 down-regulates the balance of Th17/Treg.Frontiers in immunology · 2022Article
- Evaluating the effects of curcumin nanomicelles on clinical outcome and cellular immune responses in critically ill sepsis patients: A randomized, double-blind, and placebo-controlled trial.Frontiers in nutrition · 2022Article
- CD38 Correlates with an Immunosuppressive Treg Phenotype in Lupus-Prone Mice.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesForkhead/winged helix transcription factor p3 (Foxp3) increases in CD4(+)CD25(+)Treg cells during sepsis; however, related mechanisms are unclear. Our study aimed to explore the possible molecular mechanisms of high expression of Foxp3 in Treg cells during sepsis.
methodsSepsis was induced by cecal ligation and puncture (CLP) method. CD4(+)CD25(+)Treg cells were isolated from peripheral blood and identified by flow cytometry (FCM). Treg cells were cultured with or without adenosine, adenosine agonist, adenosine antagonist, SMAD family member 3 (Smad3) agonist (transforming growth factor (TGF)-β1), or C-Jun N-Terminal Kinase (JNK) inhibitor. Expression levels of Foxp3 and activator protein 1 (AP-1) were determined. The binding of c-Fos or c-Jun to the Foxp3 promoter was then evaluated by the chromatin immunoprecipitation (ChIP) assay and quantified by quantitative real-time PCR (qRT-PCR). The mRNA and protein levels of Foxp3 were determined after transfection with siRNA against c-Fos, Fra-2, c-Jun or JunD.
resultsPharmacological inhibition of both adenosine and JNK reduced Foxp3 protein levels. JNK/AP-1 activation was involved in increased levels of Foxp3 protein in CD4(+)CD25(+)Treg cells. AP-1 regulated activity of Foxp3 promoter in Treg cells, and the induction of c-Fos or c-Jun activity leads to elevated transcription of Foxp3 gene. Knockdown of c-Fos, Fra-2, c-Jun, or JunD levels also reduced Foxp3 expression.
conclusionWe confirm that adenosine plays significant roles in the high expression of Foxp3. Adenosine promotes Foxp3 expression in Treg cells during sepsis via JNK/AP-1 pathway.
Indexed as
Identifiers
27347335PMC4891440W2463361290What 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.