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

Autor: Sara G Dosil, Sheila Lopez-Cobo, Ana Rodriguez-Galan, Irene Fernandez-Delgado, Marta Ramirez-Huesca, Paula Milan-Rois, Milagros Castellanos, Alvaro Somoza, Manuel José Gómez, Hugh T Reyburn, Mar Vales-Gomez, Francisco Sánchez Madrid, Lola Fernandez-Messina
Přispěvatelé: Fundación BBVA, Comunidad de Madrid (España), Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, Fundación Ramón Areces, Ministerio de Ciencia, Innovación y Universidades (España), Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España)
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Repositorio Institucional del Instituto Madrileño de Estudios Avanzados en Nanociencia
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Popis: 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. 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/BMD3671-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). Sí
Databáze: OpenAIRE
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