title: Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells.
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.
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares, Melchor Fernández Almagro, 3. 28029, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Mittelbrunn
authors.forename: Cristina
authors.initials: C
authors.lastname: Gutiérrez-Vázquez
authors.forename: Carolina
authors.initials: C
authors.lastname: Villarroya-Beltri
authors.forename: Susana
authors.initials: S
authors.lastname: González
authors.forename: Fátima
authors.initials: F
authors.lastname: Sánchez-Cabo
authors.forename: Manuel Ángel
authors.initials: MÁ
authors.lastname: González
authors.forename: Antonio
authors.initials: A
authors.lastname: Bernad
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánchez-Madrid
mesh_terms: D017951:Antigen Presentation / Q000502:physiology*; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015703:Antigens, CD / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D055354:Exosomes / Q000235:genetics / Q000502:physiology*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology; D055785:Gene Knockdown Techniques; D006801:Humans; D015151:Immunoblotting; D054992:Immunological Synapses / Q000502:physiology*; D019169:Jurkat Cells; D016014:Linear Models; D035683:MicroRNAs / Q000235:genetics*; D046228:Microarray Analysis; D008856:Microscopy, Fluorescence; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D060149:Tetraspanin 30
chemical_list: D015703:Antigens, CD; C554586:CD63 protein, human; D035683:MicroRNAs; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30