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题目:: MicroRNA-containing T-regulatory-cell-derived exosomes suppress pathogenic T helper 1 cells.
作者:: Okoye(Isobel S),Coomes(Stephanie M),Pelly(Victoria S),Czieso(Stephanie),Papayannopoulos(Venizelos),Tolmachova(Tanya),Seabra(Miguel C),Wilson(Mark S)
状态:: 发布时间2014-07-19 , 更新时间 2016-11-25
期刊:: Immunity
摘要:: 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.
语言:: eng
DOI:

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