Natural killer (NK) cell-derived extracellular-vesicle shuttled microRNAs control T cell responses
Natural killer (NK) cells recognize and kill target cells undergoing different types of stress. NK cells are also capable of modulating immune responses. In particular, they regulate T cell functions. Small RNA next-generation sequencing of resting and activated human NK cells and their secreted ext...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-07-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/76319 |
| _version_ | 1811253467953496064 |
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| author | Sara G Dosil Sheila Lopez-Cobo Ana Rodriguez-Galan Irene Fernandez-Delgado Marta Ramirez-Huesca Paula Milan-Rois Milagros Castellanos Alvaro Somoza Manuel José Gómez Hugh T Reyburn Mar Vales-Gomez Francisco Sánchez Madrid Lola Fernandez-Messina |
| author_facet | Sara G Dosil Sheila Lopez-Cobo Ana Rodriguez-Galan Irene Fernandez-Delgado Marta Ramirez-Huesca Paula Milan-Rois Milagros Castellanos Alvaro Somoza Manuel José Gómez Hugh T Reyburn Mar Vales-Gomez Francisco Sánchez Madrid Lola Fernandez-Messina |
| author_sort | Sara G Dosil |
| collection | DOAJ |
| description | Natural killer (NK) cells recognize and kill target cells undergoing different types of stress. NK cells are also capable of modulating immune responses. In particular, they regulate T cell functions. Small RNA next-generation sequencing of resting and activated human NK cells and their secreted extracellular vesicles (EVs) led to the identification of a specific repertoire of NK-EV-associated microRNAs and their post-transcriptional modifications signature. Several microRNAs of NK-EVs, namely miR-10b-5p, miR-92a-3p, and miR-155-5p, specifically target molecules involved in Th1 responses. NK-EVs promote the downregulation of GATA3 mRNA in CD4+ T cells and subsequent TBX21 de-repression that leads to Th1 polarization and IFN-γ and IL-2 production. NK-EVs also have an effect on monocyte and moDCs (monocyte-derived dendritic cells) function, driving their activation and increased presentation and costimulatory functions. Nanoparticle-delivered NK-EV microRNAs partially recapitulate NK-EV effects in mice. Our results provide new insights on the immunomodulatory roles of NK-EVs that may help to improve their use as immunotherapeutic tools. |
| first_indexed | 2024-04-12T16:51:25Z |
| format | Article |
| id | doaj.art-010fa4a4b14e4b4dbab5d7d3350e67db |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:51:25Z |
| publishDate | 2022-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-010fa4a4b14e4b4dbab5d7d3350e67db2022-12-22T03:24:23ZengeLife Sciences Publications LtdeLife2050-084X2022-07-011110.7554/eLife.76319Natural killer (NK) cell-derived extracellular-vesicle shuttled microRNAs control T cell responsesSara G Dosil0Sheila Lopez-Cobo1Ana Rodriguez-Galan2https://orcid.org/0000-0001-6209-782XIrene Fernandez-Delgado3Marta Ramirez-Huesca4Paula Milan-Rois5https://orcid.org/0000-0002-7043-2920Milagros Castellanos6Alvaro Somoza7Manuel José Gómez8Hugh T Reyburn9Mar Vales-Gomez10Francisco Sánchez Madrid11https://orcid.org/0000-0001-5303-0762Lola Fernandez-Messina12https://orcid.org/0000-0002-2163-8746Immunology Service, Hospital de la Princesa, Universidad Autónoma de Madrid, Instituto Investigación Sanitaria Princesa, Madrid, Spain; Intercellular Communication in the Inflammatory Response. Vascular Pathophysiology Area, National Center for Cardiovascular Research (CNIC), Madrid, Spain; Universidad Autónoma de Madrid, Madrid, SpainDepartment of Immunology and Oncology, National Centre for Biotechnology, Spanish National Research Council, Madrid, SpainImmunology Service, Hospital de la Princesa, Universidad Autónoma de Madrid, Instituto Investigación Sanitaria Princesa, Madrid, Spain; Intercellular Communication in the Inflammatory Response. Vascular Pathophysiology Area, National Center for Cardiovascular Research (CNIC), Madrid, Spain; Universidad Autónoma de Madrid, Madrid, SpainImmunology Service, Hospital de la Princesa, Universidad Autónoma de Madrid, Instituto Investigación Sanitaria Princesa, Madrid, Spain; Intercellular Communication in the Inflammatory Response. Vascular Pathophysiology Area, National Center for Cardiovascular Research (CNIC), Madrid, Spain; Universidad Autónoma de Madrid, Madrid, SpainImmunology Service, Hospital de la Princesa, Universidad Autónoma de Madrid, Instituto Investigación Sanitaria Princesa, Madrid, Spain; Intercellular Communication in the Inflammatory Response. Vascular Pathophysiology Area, National Center for Cardiovascular Research (CNIC), Madrid, Spain; Universidad Autónoma de Madrid, Madrid, SpainInstituto Madrileño de Estudios Avanzados en Nanociencia (IMDEA Nanociencia) & Nanobiotecnología (IMDEA-Nanociencia), Unidad Asociada al Centro Nacional de Biotecnología (CSIC), Madrid, SpainInstituto Madrileño de Estudios Avanzados en Nanociencia (IMDEA Nanociencia) & Nanobiotecnología (IMDEA-Nanociencia), Unidad Asociada al Centro Nacional de Biotecnología (CSIC), Madrid, SpainInstituto Madrileño de Estudios Avanzados en Nanociencia (IMDEA Nanociencia) & Nanobiotecnología (IMDEA-Nanociencia), Unidad Asociada al Centro Nacional de Biotecnología (CSIC), Madrid, SpainIntercellular Communication in the Inflammatory Response. Vascular Pathophysiology Area, National Center for Cardiovascular Research (CNIC), Madrid, SpainDepartment of Immunology and Oncology, National Centre for Biotechnology, Spanish National Research Council, Madrid, SpainDepartment of Immunology and Oncology, National Centre for Biotechnology, Spanish National Research Council, Madrid, SpainImmunology Service, Hospital de la Princesa, Universidad Autónoma de Madrid, Instituto Investigación Sanitaria Princesa, Madrid, Spain; Intercellular Communication in the Inflammatory Response. Vascular Pathophysiology Area, National Center for Cardiovascular Research (CNIC), Madrid, Spain; Universidad Autónoma de Madrid, Madrid, Spain; CIBER de Enfermedades Cardiovasculares (CIBERCV), Madrid, SpainImmunology Service, Hospital de la Princesa, Universidad Autónoma de Madrid, Instituto Investigación Sanitaria Princesa, Madrid, Spain; Intercellular Communication in the Inflammatory Response. Vascular Pathophysiology Area, National Center for Cardiovascular Research (CNIC), Madrid, Spain; Universidad Autónoma de Madrid, Madrid, Spain; CIBER de Enfermedades Cardiovasculares (CIBERCV), Madrid, SpainNatural killer (NK) cells recognize and kill target cells undergoing different types of stress. NK cells are also capable of modulating immune responses. In particular, they regulate T cell functions. Small RNA next-generation sequencing of resting and activated human NK cells and their secreted extracellular vesicles (EVs) led to the identification of a specific repertoire of NK-EV-associated microRNAs and their post-transcriptional modifications signature. Several microRNAs of NK-EVs, namely miR-10b-5p, miR-92a-3p, and miR-155-5p, specifically target molecules involved in Th1 responses. NK-EVs promote the downregulation of GATA3 mRNA in CD4+ T cells and subsequent TBX21 de-repression that leads to Th1 polarization and IFN-γ and IL-2 production. NK-EVs also have an effect on monocyte and moDCs (monocyte-derived dendritic cells) function, driving their activation and increased presentation and costimulatory functions. Nanoparticle-delivered NK-EV microRNAs partially recapitulate NK-EV effects in mice. Our results provide new insights on the immunomodulatory roles of NK-EVs that may help to improve their use as immunotherapeutic tools.https://elifesciences.org/articles/76319extracellular vesicles (EVs)exosomesmicroRNAs (miRNAs)NK cellsTh1 responsesmonocyte-derived dendritic cells |
| spellingShingle | Sara G Dosil Sheila Lopez-Cobo Ana Rodriguez-Galan Irene Fernandez-Delgado Marta Ramirez-Huesca Paula Milan-Rois Milagros Castellanos Alvaro Somoza Manuel José Gómez Hugh T Reyburn Mar Vales-Gomez Francisco Sánchez Madrid Lola Fernandez-Messina Natural killer (NK) cell-derived extracellular-vesicle shuttled microRNAs control T cell responses eLife extracellular vesicles (EVs) exosomes microRNAs (miRNAs) NK cells Th1 responses monocyte-derived dendritic cells |
| title | Natural killer (NK) cell-derived extracellular-vesicle shuttled microRNAs control T cell responses |
| title_full | Natural killer (NK) cell-derived extracellular-vesicle shuttled microRNAs control T cell responses |
| title_fullStr | Natural killer (NK) cell-derived extracellular-vesicle shuttled microRNAs control T cell responses |
| title_full_unstemmed | Natural killer (NK) cell-derived extracellular-vesicle shuttled microRNAs control T cell responses |
| title_short | Natural killer (NK) cell-derived extracellular-vesicle shuttled microRNAs control T cell responses |
| title_sort | natural killer nk cell derived extracellular vesicle shuttled micrornas control t cell responses |
| topic | extracellular vesicles (EVs) exosomes microRNAs (miRNAs) NK cells Th1 responses monocyte-derived dendritic cells |
| url | https://elifesciences.org/articles/76319 |
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