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Adenosine receptors in regulation of dendritic cell differentiation and function
Open accessAbstract
Differentiation of functional dendritic cells (DCs) critically depends on the microenvironment. DCs differentiate in hypoxic tumor sites and inflamed or damaged tissue. Because local concentrations of adenosine reach high physiologically relevant levels in these conditions, we assessed the expression of adenosine receptors and the effect of their activation on differentiation of human monocytes and mouse peritoneal macrophages and hematopoietic progenitor cells (HPCs) into myeloid DCs. Stimulation of adenosine receptors skews DC differentiation toward a distinct cell population characterized by expression of both DC and monocyte/macrophage cell surface markers. Pharmacologic analysis and experiments with cells from A2B adenosine receptor knockout mice identified A2B receptor as the mediator of adenosine effects on DCs. Unlike normal myeloid DCs, adenosine-differentiated DCs have impaired allostimulatory activity and express high levels of angiogenic, pro-inflammatory, immune suppressor, and tolerogenic factors, including VEGF, IL-8, IL-6, IL-10, COX-2, TGF-β, and IDO. They promoted tumor growth if injected into tumors implanted in mice. Using adenosine desaminase knockout animals, we showed that DCs with proangiogenic phenotype are highly abundant under conditions associated with elevated levels of extracellular adenosine in vivo. Adenosine signaling through A2B receptor is an important factor of aberrant DC differentiation and generation of tolerogenic, angiogenic, and proinflammatory cells.
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“The engagement of adenosine 2A receptor (A2AR) with adenosine elicits immunoinhibitory effects: suppressing the activities of tumor-infiltrating CD8+ T cells and hampering the function and differentiation of DCs [333, 334].”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [333]
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Metadata
- Authors
- Novitskiy, S. V., Ryzhov, S., Zaynagetdinov, R., Goldstein, A. E., Huang, Y., Tikhomirov, O. Y., Blackburn, M. R., Biaggioni, I., Carbone, D. P., Feoktistov, I., & Dikov, M. M.
- Affiliations
- Division of Hematology/Oncology,
- Department of Medicine,
- Vanderbilt University (US)
- Department of Biochemistry and Molecular Biology, University of Texas-Houston Medical School
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2008-09-01
- Volume
- 112
- Issue
- 5
- Pages
- 1822-1831
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC2518889
- OpenAlex
- W1981552113
- Cited by
- 430
- References
- 44
- Citations by year
- 2026: 17 · 2025: 18 · 2024: 28 · 2023: 40 · 2022: 33 · 2021: 33 · 2020: 43 · 2019: 23 · 2018: 24 · 2017: 27 · 2016: 17 · 2015: 13 · 2014: 24 · 2013: 18 · 2012: 18
- FWCI
- 11.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Histiocytosis Association
- Vanderbilt University
- Vanderbilt-Ingram Cancer Center (5P30-CA068485, CA100562, CA068485)
- National Institutes of Health (CA-068485)
- National Heart, Lung, and Blood Institute (R01HL070952, HL70952, R01HL076306, R01HL070073, HL76306)
- National Cancer Institute (R01CA100562, CA76321, R01CA076321, CA100562, P30CA068485)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- adenosine receptors, adenosine A2B receptor, dendritic cell differentiation, myeloid dendritic cells, adenosine signaling, monocytes, peritoneal macrophages, hematopoietic progenitor cells, tumor microenvironment, hypoxia, allostimulatory activity, angiogenic factors, immunosuppression, tumor growth, vascular endothelial growth factor, IDO, TGF-beta
- MeSH terms
- Adenosine, Adenosine Deaminase, Animals, Base Sequence, Cell Differentiation, Dendritic Cells, Humans, Immune Tolerance, Male, Mice, Inbred C57BL, Neoplasms, Experimental, Neovascularization, Pathologic, Signal Transduction, DNA Primers, Receptors, Purinergic P1, Mice, Knockout, Inflammation Mediators, Receptor, Adenosine A2B, Mice, Purinergic P1 Receptor Antagonists, Adenosine A2 Receptor Antagonists
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