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 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-gamma 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.

Automated summary

NK cells and their secreted EVs have immunomodulatory roles, promoting Th1 responses and activating monocytes and moDCs. MicroRNAs of NK-EVs target molecules involved in Th1 responses and partially recapitulate their effects in mice.