ArticleImmunity, inflammation and disease2018
ATP promotes immunosuppressive capacities of mesenchymal stromal cells by enhancing the expression of indoleamine dioxygenase.
Article in Immunity, inflammation and disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 15 citations in OpenAlex.
- Kynurenine Pathway Metabolites as Mediators of Exercise-Induced Mood Enhancement, Fatigue Resistance, and Neuroprotection.International journal of molecular sciences · 2025Review
- Immunomodulatory and cardio-protective effects of differentially originated multipotent mesenchymal stroma cells during polymicrobial sepsis in mice.European journal of trauma and emergency surgery : official publication of the European Trauma Society · 2025Article
- Mesenchymal Stem Cells and Purinergic Signaling in Autism Spectrum Disorder: Bridging the Gap between Cell-Based Strategies and Neuro-Immune Modulation.Biomedicines · 2024Review
- Roles of extracellular adenosine triphosphate on the functions of periodontal ligament cells.BDJ open · 2023Review
- The Role of Purinergic P2X7 Receptor in Inflammation and Cancer: Novel Molecular Insights and Clinical Applications.Cancers · 2022Review
- Role of indoleamine 2,3-dioxygenase in ischemia-reperfusion injury of renal tubular epithelial cells.Molecular medicine reports · 2021Article
- Immortalization of Mesenchymal Stromal Cells by TERT Affects Adenosine Metabolism and Impairs their Immunosuppressive Capacity.Stem cell reviews and reports · 2020Article
- Mesenchymal Stromal Cell Immunology for Efficient and Safe Treatment of Osteoarthritis.Frontiers in cell and developmental biology · 2020Review
- Surgical trauma-induced immunosuppression in cancer: Recent advances and the potential therapies.Clinical and translational medicine · 2020Review
- Defective Proliferation and Osteogenic Potential with Altered Immunoregulatory phenotype of Native Bone marrow-Multipotential Stromal Cells in Atrophic Fracture Non-Union.Scientific reports · 2019Article
- ATP promotes immunosuppressive capacities of mesenchymal stromal cells by enhancing the expression of indoleamine dioxygenase.Immunity, inflammation and disease · 2018Article
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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
introductionMSCs are often found within tumors, promote cancer progression and enhance metastasis. MSCs can act as immuosuppressive cells, partially due to the expression of the enzyme indoleamine dioxygenase (IDO) which converts tryptophan to kynurenine. Decreased concentration of tryptophan and increased kynurenine, both interfere with effective immune response. Damage associated molecular patterns (DAMPs) including ATP are found within the tumor microenvironment, attract MSCs, and influence their biology.
methodsBone marrow derived MSCs were exposed to ATP for 4 days, in the presence of 100 ng IFNγ/mL. Intracellular expression of IDO in MSCs was assessed by FACS. Conditioned media from thus stimulated MSCs was analyzed for kynurenine content and its suppressive effect on lymphocyte proliferation. Apyrase or P2 × 7-receptor antagonist (AZ 11645373) were applied in order to inhibit ATP induced effect on MSCs.
resultsWe demonstrate, that ATP at concentrations between 0.062 and 0.5 mM increases dose dependently the expression of IDO in MSCs with subsequent increased kynurenine concentrations within the supernatant at about 60%. This effect could be abolished completely in the presence of ATP degrading enzyme (apyrase) or when MSCs were pretreated with a P2 × 7-receptor antagonist (AZ 11645373). Consistently, supernatants from MSCs stimulated with ATP, inhibited lymphocyte proliferation from 65% to 16%.
conclusionsWe characterized ATP as a DAMP family member responsible for necrosis-induced immunomodulation. Given the increased concentration of DAMPs within tumor tissue and the fact that DAMPs can act as chemotattractants to MSCs, our results have implications for therapeutic strategies targeting the tumor microenvironment.
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