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...

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Published in:eLife 2022-07, Vol.11
Main Authors: Dosil, Sara G, Lopez-Cobo, Sheila, Rodriguez-Galan, Ana, Fernandez-Delgado, Irene, Ramirez-Huesca, Marta, Milan-Rois, Paula, Castellanos, Milagros, Somoza, Alvaro, Gómez, Manuel José, Reyburn, Hugh T, Vales-Gomez, Mar, Sánchez Madrid, Francisco, Fernandez-Messina, Lola
Format: Article
Language:English
Subjects:
Dendritic cells
exosomes
extracellular vesicles (EVs)
Genetic transcription
Immune response
Immunology and Inflammation
Killer cells
MicroRNA
microRNAs (miRNAs)
monocyte-derived dendritic cells
NK cells
T cells
Th1 responses
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Summary: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.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.76319