Enhanced expression of natural cytotoxicity receptors on cytokine-induced memory-like natural killer cells correlates with effector function
IntroductionNatural killer (NK) cells are a key component of the innate immune system, involved in defending the host against virus-infected cells and tumor immunosurveillance. Under in vitro culture conditions, IL-12/15/18 can induce a memory-like phenotype in NK cells. These cytokine-induced memor...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1256404/full |
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| author | Sofía Carreira-Santos Nelson López-Sejas Marina González-Sánchez Eva Sánchez-Hernández Alejandra Pera Alejandra Pera Fakhri Hassouneh Esther Durán Rafael Solana Rafael Solana Rafael Solana Javier G. Casado Javier G. Casado Javier G. Casado Javier G. Casado Raquel Tarazona Raquel Tarazona |
| author_facet | Sofía Carreira-Santos Nelson López-Sejas Marina González-Sánchez Eva Sánchez-Hernández Alejandra Pera Alejandra Pera Fakhri Hassouneh Esther Durán Rafael Solana Rafael Solana Rafael Solana Javier G. Casado Javier G. Casado Javier G. Casado Javier G. Casado Raquel Tarazona Raquel Tarazona |
| author_sort | Sofía Carreira-Santos |
| collection | DOAJ |
| description | IntroductionNatural killer (NK) cells are a key component of the innate immune system, involved in defending the host against virus-infected cells and tumor immunosurveillance. Under in vitro culture conditions, IL-12/15/18 can induce a memory-like phenotype in NK cells. These cytokine-induced memory-like (CIML) NK cells possess desirable characteristics for immunotherapies, including a longer lifespan and increased cytotoxicity.MethodsIn this study, NK cells were isolated from peripheral blood of healthy donors and stimulated with IL-12/15/18 to induce a memory-like phenotype or with IL-15 alone as a control. After seven days of culture, multiparametric flow cytometry analysis was performed to evaluate the phenotypic and functional profiles of CIML and control NK cells.ResultsOur results showed a significantly higher expression of CD25, CD69, NKG2D, NKp30, NKp44, NKp46, TACTILE, and Granzyme B in CIML NK cells compared to control NK cells. In contrast, KIR2D expression was significantly lower in CIML NK cells than in control NK cells. Moreover, functional experiments demonstrated that CIML NK cells displayed enhanced degranulation capacity and increased intracellular IFN-γ production against the target cell line K562. Interestingly, the degranulation capacity of CIML NK cells was positively correlated with the expression of the activating receptors NKp46 and NKp30, as well as with the inhibitory receptor TACTILE.DiscussionIn conclusion, this study provides a deep phenotypic characterization of in vitro-expanded CIML NK cells. Moreover, the correlations found between NK cell receptors and degranulation capacity of CIML NK cells allowed the identification of several biomarkers that could be useful in clinical settings. |
| first_indexed | 2024-03-11T18:17:07Z |
| format | Article |
| id | doaj.art-52eb3c2b2c4c4119bfdeb8dd97eb00b3 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-11T18:17:07Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-52eb3c2b2c4c4119bfdeb8dd97eb00b32023-10-16T05:57:50ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-10-011410.3389/fimmu.2023.12564041256404Enhanced expression of natural cytotoxicity receptors on cytokine-induced memory-like natural killer cells correlates with effector functionSofía Carreira-Santos0Nelson López-Sejas1Marina González-Sánchez2Eva Sánchez-Hernández3Alejandra Pera4Alejandra Pera5Fakhri Hassouneh6Esther Durán7Rafael Solana8Rafael Solana9Rafael Solana10Javier G. Casado11Javier G. Casado12Javier G. Casado13Javier G. Casado14Raquel Tarazona15Raquel Tarazona16Immunology Unit, Department of Physiology, Universidad de Extremadura, Cáceres, SpainImmunology Unit, Department of Physiology, Universidad de Extremadura, Cáceres, SpainImmunology Unit, Department of Physiology, Universidad de Extremadura, Cáceres, SpainImmunology Unit, Department of Physiology, Universidad de Extremadura, Cáceres, SpainImmunology and Allergy Group (GC01), Maimonides Biomedical Research Institute of Córdoba (IMIBIC), Córdoba, SpainDepartment of Cell Biology, Physiology and Immunology, Universidad de Córdoba, Córdoba, SpainImmunology and Allergy Group (GC01), Maimonides Biomedical Research Institute of Córdoba (IMIBIC), Córdoba, SpainAnatomy and Comparative Pathological Anatomy Unit, Department of Animal Medicine, Faculty of Veterinary Medicine, Universidad de Extremadura, Cáceres, SpainImmunology and Allergy Group (GC01), Maimonides Biomedical Research Institute of Córdoba (IMIBIC), Córdoba, SpainDepartment of Cell Biology, Physiology and Immunology, Universidad de Córdoba, Córdoba, SpainImmunology and Allergy Service, Reina Sofia University Hospital, Cordoba, SpainImmunology Unit, Department of Physiology, Universidad de Extremadura, Cáceres, SpainCentro de Investigación Biomédica En Red (CIBER) de Enfermedades Cardiovasculares, Instituto de Salud Carlos III (ISCIII), Madrid, SpainRICORS-TERAV Network, Instituto de Salud Carlos III (ISCIII), Madrid, SpainInstitute of Molecular Pathology Biomarkers, Universidad de Extremadura, Cáceres, SpainImmunology Unit, Department of Physiology, Universidad de Extremadura, Cáceres, SpainInstitute of Molecular Pathology Biomarkers, Universidad de Extremadura, Cáceres, SpainIntroductionNatural killer (NK) cells are a key component of the innate immune system, involved in defending the host against virus-infected cells and tumor immunosurveillance. Under in vitro culture conditions, IL-12/15/18 can induce a memory-like phenotype in NK cells. These cytokine-induced memory-like (CIML) NK cells possess desirable characteristics for immunotherapies, including a longer lifespan and increased cytotoxicity.MethodsIn this study, NK cells were isolated from peripheral blood of healthy donors and stimulated with IL-12/15/18 to induce a memory-like phenotype or with IL-15 alone as a control. After seven days of culture, multiparametric flow cytometry analysis was performed to evaluate the phenotypic and functional profiles of CIML and control NK cells.ResultsOur results showed a significantly higher expression of CD25, CD69, NKG2D, NKp30, NKp44, NKp46, TACTILE, and Granzyme B in CIML NK cells compared to control NK cells. In contrast, KIR2D expression was significantly lower in CIML NK cells than in control NK cells. Moreover, functional experiments demonstrated that CIML NK cells displayed enhanced degranulation capacity and increased intracellular IFN-γ production against the target cell line K562. Interestingly, the degranulation capacity of CIML NK cells was positively correlated with the expression of the activating receptors NKp46 and NKp30, as well as with the inhibitory receptor TACTILE.DiscussionIn conclusion, this study provides a deep phenotypic characterization of in vitro-expanded CIML NK cells. Moreover, the correlations found between NK cell receptors and degranulation capacity of CIML NK cells allowed the identification of several biomarkers that could be useful in clinical settings.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1256404/fullNK cellsmemory-likecytokine-induced memory-like NK cellsNKG2Dnatural cytotoxicity receptorsdegranulation capacity |
| spellingShingle | Sofía Carreira-Santos Nelson López-Sejas Marina González-Sánchez Eva Sánchez-Hernández Alejandra Pera Alejandra Pera Fakhri Hassouneh Esther Durán Rafael Solana Rafael Solana Rafael Solana Javier G. Casado Javier G. Casado Javier G. Casado Javier G. Casado Raquel Tarazona Raquel Tarazona Enhanced expression of natural cytotoxicity receptors on cytokine-induced memory-like natural killer cells correlates with effector function Frontiers in Immunology NK cells memory-like cytokine-induced memory-like NK cells NKG2D natural cytotoxicity receptors degranulation capacity |
| title | Enhanced expression of natural cytotoxicity receptors on cytokine-induced memory-like natural killer cells correlates with effector function |
| title_full | Enhanced expression of natural cytotoxicity receptors on cytokine-induced memory-like natural killer cells correlates with effector function |
| title_fullStr | Enhanced expression of natural cytotoxicity receptors on cytokine-induced memory-like natural killer cells correlates with effector function |
| title_full_unstemmed | Enhanced expression of natural cytotoxicity receptors on cytokine-induced memory-like natural killer cells correlates with effector function |
| title_short | Enhanced expression of natural cytotoxicity receptors on cytokine-induced memory-like natural killer cells correlates with effector function |
| title_sort | enhanced expression of natural cytotoxicity receptors on cytokine induced memory like natural killer cells correlates with effector function |
| topic | NK cells memory-like cytokine-induced memory-like NK cells NKG2D natural cytotoxicity receptors degranulation capacity |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1256404/full |
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