Natural killer (NK) cell-derived extracellular-vesicle shuttled microRNAs control T cell responses
- Universidad Autónoma de Madrid, Spain
- INSERM U932, Institut Curie, PSL Research University, France
- National Center for Cardiovascular Research, Spain
- Unidad Asociada al Centro Nacional de Biotecnología, Spain
- Spanish National Research Council, Spain
Abstract
Natural killer (NK) cells recognise 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 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 function, driving their activation and increased presentation and co-stimulatory 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.
Data availability
Sequencing data have been deposited in the Gene Expression Omnibus and are available to readers under record GSE185171. EV isolation procedures are available at EV‐TRACK knowledgebase (EV‐TRACK ID: EV210234.
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Natural killer (NK) cell-derived extracellular-vesicle shuttled microRNAs control T cell responsesNCBI Gene Expression Omnibus, GSE185171.
Article and author information
Author details
Ana Rodriguez-Galan
Francisco Sánchez Madrid
Lola Fernandez-Messina
Funding
Spanish National Plan for Scientific and Technical Research and Innovation (PD1-2020-120412RB-100)
- Francisco Sánchez Madrid
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experimental methods and protocols were approved by the CNIC and the Comunidad Autónoma de Madrid and conformed to European Commission guidelines and regulations (PROEX-206.1/20)
Copyright
© 2022, Dosil et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Natural killer (NK) cell-derived extracellular-vesicle shuttled microRNAs control T cell responses
eLife 11:e76319.
https://doi.org/10.7554/eLife.76319
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