• Isobel S Okoye, Stephanie M Coomes, Victoria S Pelly, Stephanie Czieso, Venizelos Papayannopoulos, Tanya Tolmachova, Miguel C Seabra, and Mark S Wilson.
• Division of Molecular Immunology, MRC, National Institute for Medical Research, London NW7 1AA, UK.
• Immunity. 2014 Jul 17;41(1):89-103.

AbstractFoxp3(+) 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.Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

43 keywords...

hide…