Natural killer (NK) cell-derived extracellular-vesicle shuttled microRNAs control T cell responses

Dosil, S. G.; Lopez-Cobo, S.; Rodriguez-Galan, A.; Fernandez-Delgado, I.; Ramirez-Huesca, M.; Milan-Rois, P.; Castellanos, M.; Somoza, A.; Gomez, M. J.; Reyburn, H. T.; Vales-Gomez, M.; Sanchez Madrid, F.; Fernandez-Messina, L.

doi:10.1101/2022.01.05.475119

bioRxiv · 10.1101/2022.01.05.475119

Natural killer (NK) cell-derived extracellular-vesicle shuttled microRNAs control T cell responses

Dosil, S. G.·Lopez-Cobo, S.·Rodriguez-Galan, A.·Fernandez-Delgado, I.·Ramirez-Huesca, M.·Milan-Rois, P.·Castellanos, M.·Somoza, A.·Gomez, M. J.·Reyburn, H. T.·Vales-Gomez, M.·Sanchez Madrid, F.·Fernandez-Messina, L.

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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 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 GATA-3 mRNA in CD4+ T cells and subsequent T-bet de-repression that leads to Th1 polarization and IFN-{gamma} 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 vivo. Our results provide new insights on the immunomodulatory roles of NK-EVs that may help to improve their use as immunotherapeutic tools.

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Dosil, S. G., Lopez-Cobo, S., Rodriguez-Galan, A., Fernandez-Delgado, I., Ramirez-Huesca, M., Milan-Rois, P., Castellanos, M., Somoza, A., Gomez, M. J., Reyburn, H. T., Vales-Gomez, M., Sanchez Madrid, F., Fernandez-Messina, L.. 2022-01-07. Natural killer (NK) cell-derived extracellular-vesicle shuttled microRNAs control T cell responses. https://doi.org/10.1101/2022.01.05.475119

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