RT Journal Article
T1 Natural killer (NK) cell-derived extracellular-vesicle shuttled microRNAs control T cell responses
A1 Dosil, Sara
A1 López-Cobo, Sheila
A1 Rodríguez-Galán, Ana
A1 Fernandez-Delgado, Irene
A1 Ramirez-Huesca, Marta
A1 Milan-Rois, Paula
A1 Castellanos, Milagros
A1 Somoza, Álvaro
A1 Gómez, Manuel José
A1 Reyburn, Hugh
A1 Vales-Gómez, Mar
A1 Sánchez Madrid, Francisco
A1 Fernández Messina, Lola María
AB 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.
PB eLife Sciences Publications
SN 2050-084X
YR 2022
FD 2022
LK https://hdl.handle.net/20.500.14352/97242
UL https://hdl.handle.net/20.500.14352/97242
LA eng
NO Sara G DosilSheila Lopez-CoboAna Rodriguez-GalanIrene Fernandez-DelgadoMarta Ramirez-HuescaPaula Milan-RoisMilagros CastellanosAlvaro SomozaManuel José GómezHugh T ReyburnMar Vales-GomezFrancisco Sánchez MadridLola Fernandez-Messina (2022) Natural killer (NK) cell-derived extracellular-vesicle shuttled microRNAs control T cell responses eLife 11:e76319.
NO AcknowledgementsNGS experiments were performed in the CNIC Genomics Unit (Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain) and analysed by the CNIC Bioinformatics Unit. This manuscript was funded by grants PDI-2020-120412RB-I00 and PDC2021- 121719-I00 (FS-M) and PID2020-119352RB-I00 (AS) from the Spanish Ministry of Economy and Competitiveness; CAM (S2017/BMD-3671-INFLAMUNE-CM) from the Comunidad de Madrid (FS-M). CIBERCV (CB16/11/00272) and BIOIMID PIE13/041 from the Instituto de Salud Carlos. The current research has received funding from 'la Caixa' Foundation under the project code HR17-00016. Grants from Ramón Areces Foundation 'Ciencias de la Vida y de la Salud' (XIX Concurso-2018) and from Ayuda Fundación BBVA y Equipo de Investigación Científica (BIOMEDICINA-2018) (to FSM). The CNIC is supported by the Ministerio de Ciencia, Innovacion y Universidades and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015–0505). IMDEA Nanociencia acknowledges support from the ‘Severo Ochoa’ Programme for Centres of Excellence in R&D (MINECO, CEX2020-001039-S). SGD is supported by a grant from the Spanish Ministry of Universities. Authors thank Dr Miguel Vicente-Manzanares for critical review and editing. We also thank Dr Francisco Urbano and Dr Covadonga Aguado for their support with EM (TEM facilities, Universidad Autónoma de Madrid).
NO Centro Nacional de Investigaciones Cardiovasculares
NO Comunidad de Madrid
NO Ministerio de Economía y Competitividad (España)
NO Ministerio de Ciencia, Innovación y Universidades (España)
NO Instituto de Salud Carlos III
DS Docta Complutense
RD 9 abr 2025