Regulatory T cell-derived extracellular vesicles modify dendritic cell function

Sim L. Tung, Dominic A. Boardman, Monica Sen, Marilena Letizia, Qi Peng, Nicole Cianci, Laura Dioni, Leo M. Carlin, Robert Lechler, Valentina Bollati, Giovanna Lombardi, Lesley A. Smyth*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    135 Citations (Scopus)
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    Abstract

    Regulatory T cells (Treg) are a subpopulation of T cells that maintain tolerance to self and limit other immune responses. They achieve this through different mechanisms including the release of extracellular vesicles (EVs) such as exosomes as shown by us, and others. One of the ways that Treg derived EVs inhibit target cells such as effector T cells is via the transfer of miRNA. Another key target for the immunoregulatory function of Tregs is the dendritic cells (DCs). In this study we demonstrate directly, and for the first time, that miRNAs are transferred from Tregs to DCs via Treg derived EVs. In particular two miRNAs, namely miR-150-5p and miR-142-3p, were increased in DCs following their interaction with Tregs and Treg derived exosomes. One of the consequences for DCs following the acquisition of miRNAs contained in Treg derived EVs was the induction of a tolerogenic phenotype in these cells, with increased IL-10 and decreased IL-6 production being observed following LPS stimulation. Altogether our findings provide data to support the idea that intercellular transfer of miRNAs via EVs may be a novel mechanism by which Tregs regulate DC function and could represent a mechanism to inhibit immune reactions in tissues.

    Original languageEnglish
    Article number6065
    JournalScientific Reports
    Volume8
    Issue number1
    Early online date17 Apr 2018
    DOIs
    Publication statusPublished - Dec 2018

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