ArticleJournal of immunology (Baltimore, Md. : 1950)2019
The cAMP-Adenosine Feedback Loop Maintains the Suppressive Function of Regulatory T Cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Peptide hormones and bile acids shaping immune tolerance of the liver: implications and applications.Protein & cell · 2026Review
- Purin Metabolism Is Crucial for Regulatory T Cell Stability and Function.European journal of immunology · 2025Review
- Comprehensive single-cell profiling of monocytes in HLA-B27-positive ankylosing spondylitis with acute anterior uveitis.MedComm · 2024Article
- Beyond Immune Balance: The Pivotal Role of Decidual Regulatory T Cells in Unexplained Recurrent Spontaneous Abortion.Journal of inflammation research · 2024Review
- The Role of Regulatory T Cells in Cancer Treatment Resistance.International journal of molecular sciences · 2023Review
- Treg-specific deletion of the phosphatase SHP-1 impairs control of inflammationFrontiers in immunology · 2023Article
- Transcriptional Behavior of Regulatory T Cells Predicts IBD Patient Responses to Vedolizumab Therapy.Inflammatory bowel diseases · 2022Article
- Melatonin, an endogenous hormone, modulates Th17 cells via the reactive-oxygen species/TXNIP/HIF-1α axis to alleviate autoimmune uveitis.Journal of neuroinflammation · 2022Article
- Stereotypic Expansion of T Regulatory and Th17 Cells during Infancy Is Disrupted by HIV Exposure and Gut Epithelial Damage.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- CD39/CD73 Dysregulation of Adenosine Metabolism Increases Decidual Natural Killer Cell Cytotoxicity: Implications in Unexplained Recurrent Spontaneous Abortion.Frontiers in immunology · 2022Article
- Extracellular cAMP-Adenosine Pathway Signaling: A Potential Therapeutic Target in Chronic Inflammatory Airway Diseases.Frontiers in immunology · 2022Review
- Decoding the Key Functional Combined Components Group and Uncovering the Molecular Mechanism of Longdan Xiegan Decoction in Treating Uveitis.Drug design, development and therapy · 2022Article
- TGF-β-induced CD4+ FoxP3+ regulatory T cell-derived extracellular vesicles modulate Notch1 signaling through miR-449a and prevent collagen-induced arthritis in a murine model.Cellular & molecular immunology · 2021Article
- Immunosuppressive metabolites in tumoral immune evasion: redundancies, clinical efforts, and pathways forward.Journal for immunotherapy of cancer · 2021Review
- A Structure-Guided Delineation of FOXP3 Regulation Mechanism in IPEX.Advances in experimental medicine and biology · 2021Article
- Understanding and Targeting Human Cancer Regulatory T Cells to Improve Therapy.Advances in experimental medicine and biology · 2021Article
- Intestinal Regulatory T Cells.Advances in experimental medicine and biology · 2021Article
- Tregs in Autoimmune Uveitis.Advances in experimental medicine and biology · 2021Article
- Regulatory T Cells: Concept, Classification, Phenotype, and Biological Characteristics.Advances in experimental medicine and biology · 2021Article
- The Association of Gut Microbiota and Treg Dysfunction in Autoimmune Diseases.Advances in experimental medicine and biology · 2021Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Therapeutic manipulation of regulatory T cells (Tregs) has been regarded as a promising approach for the treatment of immune disorders. However, a better understanding of the immunomodulatory mechanisms of Tregs and new safe and effective methods to improve the therapeutic effects of Tregs are highly desired. In this study, we have identified the key roles of a cAMP-adenosine positive feedback loop in the immunomodulatory function of Tregs. Adult male C57BL/6J mice were used for an experimental autoimmune uveitis (EAU) model, Tregs, and uveitogenic T cells (UTs). In established EAU, induced Tregs (iTregs) administration alleviated the inflammatory response. In vitro, iTregs inhibited UTs proliferation and inflammatory cytokine production. Mechanistically, cAMP is partially responsible for iTreg-mediated inhibition on UTs. Importantly, intracellular cAMP regulates CD39 expression and CD39-dependent adenosine production in iTregs, and cAMP directly participates in iTreg-derived adenosine production by a CD39 signaling-independent extracellular cAMP-adenosine pathway. Moreover, extracellular adenosine increases the intracellular cAMP level in Tregs. More importantly, increasing the cAMP level in iTregs before transfer improves their therapeutic efficacy in established EAU. Notably, the cAMP-adenosine loop exists in both iTregs and naturally occurring Tregs. These findings provide new insights into the immunosuppressive mechanisms of Tregs and suggest a new strategy for improving the therapeutic efficacy of Tregs in established autoimmune disease.
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