MicroRNA-containing T-regulatory-cell-derived Exosomes Suppress Pathogenic T Helper 1 Cells

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2014 Jul 19

PMID 25035954

Citations 294

Authors

Isobel S Okoye

Stephanie M Coomes

Victoria S Pelly

Stephanie Czieso

Venizelos Papayannopoulos

Tanya Tolmachova

Miguel C Seabra

Mark S Wilson

Affiliations

Soon will be listed here.

Abstract

Foxp3(+) T regulatory (Treg) cells prevent inflammatory disease but the mechanistic basis of suppression is not understood completely. Gene silencing by RNA interference can act in a cell-autonomous and non-cell-autonomous manner, providing mechanisms of intercellular regulation. Here, we demonstrate that non-cell-autonomous gene silencing, mediated by miRNA-containing exosomes, is a mechanism employed by Treg cells to suppress T-cell-mediated disease. Treg cells transferred microRNAs (miRNA) to various immune cells, including T helper 1 (Th1) cells, suppressing Th1 cell proliferation and cytokine secretion. Use of Dicer-deficient or Rab27a and Rab27b double-deficient Treg cells to disrupt miRNA biogenesis or the exosomal pathway, respectively, established a requirement for miRNAs and exosomes for Treg-cell-mediated suppression. Transcriptional analysis and miRNA inhibitor studies showed that exosome-mediated transfer of Let-7d from Treg cell to Th1 cells contributed to suppression and prevention of systemic disease. These studies reveal a mechanism of Treg-cell-mediated suppression mediated by miRNA-containing exosomes.

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