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Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells

Author

Listed:
  • María Mittelbrunn

    (Centro Nacional de Investigaciones Cardiovasculares, Melchor Fernández Almagro)

  • Cristina Gutiérrez-Vázquez

    (Centro Nacional de Investigaciones Cardiovasculares, Melchor Fernández Almagro)

  • Carolina Villarroya-Beltri

    (Centro Nacional de Investigaciones Cardiovasculares, Melchor Fernández Almagro)

  • Susana González

    (Centro Nacional de Investigaciones Cardiovasculares, Melchor Fernández Almagro)

  • Fátima Sánchez-Cabo

    (Centro Nacional de Investigaciones Cardiovasculares, Melchor Fernández Almagro)

  • Manuel Ángel González

    (Centro Nacional de Investigaciones Cardiovasculares, Melchor Fernández Almagro)

  • Antonio Bernad

    (Centro Nacional de Investigaciones Cardiovasculares, Melchor Fernández Almagro)

  • Francisco Sánchez-Madrid

    (Centro Nacional de Investigaciones Cardiovasculares, Melchor Fernández Almagro
    Servicio de Inmunología, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa, Diego de León)

Abstract

The immune synapse is an exquisitely evolved means of communication between T cells and antigen-presenting cells (APCs) during antigen recognition. Recent evidence points to the transfer of RNA via exosomes as a novel mode of intercellular communication. Here we show that exosomes of T, B and dendritic immune cells contain microRNA (miRNA) repertoires that differ from those of their parent cells. We investigate whether miRNAs are exchanged during cognate immune interactions, and demonstrate the existence of antigen-driven unidirectional transfer of miRNAs from the T cell to the APC, mediated by the delivery of CD63+ exosomes on immune synapse formation. Inhibition of exosome production by targeting neutral sphingomyelinase-2 impairs transfer of miRNAs to APCs. Moreover, miRNAs transferred during immune synapsis are able to modulate gene expression in recipient cells. Thus, our results support a mechanism of cellular communication involving antigen-dependent, unidirectional intercellular transfer of miRNAs by exosomes during immune synapsis.

Suggested Citation

  • María Mittelbrunn & Cristina Gutiérrez-Vázquez & Carolina Villarroya-Beltri & Susana González & Fátima Sánchez-Cabo & Manuel Ángel González & Antonio Bernad & Francisco Sánchez-Madrid, 2011. "Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells," Nature Communications, Nature, vol. 2(1), pages 1-10, September.
    • Handle: RePEc:nat:natcom:v:2:y:2011:i:1:d:10.1038_ncomms1285
    DOI: 10.1038/ncomms1285
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    Cited by:

    1. Sophie L Wardle & Mark E S Bailey & Audrius Kilikevicius & Dalia Malkova & Richard H Wilson & Tomas Venckunas & Colin N Moran, 2015. "Plasma MicroRNA Levels Differ between Endurance and Strength Athletes," PLOS ONE, Public Library of Science, vol. 10(4), pages 1-15, April.
    2. Jinhong Xu & Le Cui & Jiaqi Wang & Shasha Zheng & Huahua Zhang & Shuo Ke & Xiaoqin Cao & Yanteng Shi & Jing Li & Ke Zen & Antonio Vidal-Puig & Chen-Yu Zhang & Liang Li & Xiaohong Jiang, 2023. "Cold-activated brown fat-derived extracellular vesicle-miR-378a-3p stimulates hepatic gluconeogenesis in male mice," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    3. Pablo F. Céspedes & Ashwin Jainarayanan & Lola Fernández-Messina & Salvatore Valvo & David G. Saliba & Elke Kurz & Audun Kvalvaag & Lina Chen & Charity Ganskow & Huw Colin-York & Marco Fritzsche & Yan, 2022. "T-cell trans-synaptic vesicles are distinct and carry greater effector content than constitutive extracellular vesicles," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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