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

By M. Mittelbrunn, Cristina Gutiérrez-Vázquez, Carolina Villarroya-Beltri, S. González, Fátima Sánchez-Cabo, Manuel A. González, A. Bernad, F. Sánchez‐Madrid. Nature Communications, 2011

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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.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/926feab85b5973119d9ba6adfca8ee35a6021781

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Citations in the corpus

Biological properties of extracellular vesicles and their physiological functions (2015, background): “Although this enrichment could occur because of a size restriction, there is a specific repertoire of miRNAs selectively exported to EVs even among small RNA species, whereas other miRNAs are usually excluded (164,166,179,180), indicating that an active sorting mechanism occurs at RNA level.”
Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. (2012, background): “certain RNAs are present at significantly different levels compared to the total cell lysate from the originating cells [22–24].”
An overview of microRNAs (2015, background): “miRNAs can be taken up by target cells and mediate target gene repression[228-230].”
Cardiac fibroblast-derived microRNA passenger strand-enriched exosomes mediate cardiomyocyte hypertrophy. (2014, neutral): “Interestingly, miR-21* was found to be abundant in T cell– and B cell–derived exosomes, but miR-21* was more abundant in cells than in exosomes (30).”
SORTING IT OUT: REGULATION OF EXOSOME LOADING (2014, background): “The RNA content of exosomes is enriched in small RNA species including miRNAs, which have been demonstrated to be functional in the recipient cells [3, 4, 30, 58, 59].”
Active loading into extracellular vesicles significantly improves the cellular uptake and photodynamic effect of porphyrins. (2015, background): “Moreover, off-target effects are less likely when using EVs as they often specifically transit to their target cells [11,13].”
Lipids in exosomes: Current knowledge and the way forward. (2017, background): “Later, a similar effect of nSMasewas reported in the human embryonic kidney cell line HEK293 [75] and in T-cells [76].”