Cited by 441Adenosine and Purinergic SignalingImmunotherapy and Immune ResponsesImmune cells in cancer

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Adenosine receptors in regulation of dendritic cell differentiation and function

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Novitskiy, Sergey V., Ryzhov, Sergey, Zaynagetdinov, Rinat, Goldstein, Anna E., Huang, Yuhui, Tikhomirov, Oleg Y., Blackburn, Michael R., Biaggioni, Italo, Carbone, David P., Feoktistov, Igor, Dikov, Mikhail M.·2008·Blood

DOI 10.1182/blood-2008-02-136325PMC PMC2518889

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Abstract

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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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: Novitskiy, Sergey V.
Ryzhov, Sergey
Zaynagetdinov, Rinat
Huang, Yuhui
Blackburn, Michael R.
Biaggioni, Italo
Carbone, David P.
Feoktistov, Igor
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
DOI: 10.1182/blood-2008-02-136325
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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Adenosine receptors in regulation of dendritic cell differentiation and function

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