MicroRNA-Containing T-Regulatory-Cell-Derived Exosomes Suppress Pathogenic T Helper 1 Cells

Abstract

SummaryFoxp3+ 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.

CD4+VEGFR1HIGH T cell as a novel Treg subset regulates inflammatory bowel disease in lymphopenic mice

“…55 Some papers have reported that microRNA-containing or Fas ligand-expressing exosomes from Tregs or other tissues could mediate effector T-cell apoptosis. [56][57][58] Taken together, CD4 1 VEGFR1 high T-cell-mediated suppression might be exerted in various ways depending on the microenvironment, so that further studies to identify soluble factor(s) responsible for the suppressive activity should be considered under various circumstances. IBD is a chronic and relapsing inflammatory disorder and one of the CD4 1 T-cell-mediated autoimmune diseases.…”

Extracellular vesicles swarm the cancer microenvironment: from tumor–stroma communication to drug intervention

“…In addition, recent data showed that the composition of EVs may also depend on the hypoxic status of glioma cells 41 . In using glioma cell lines and patient- 59 . There is now a growing body of evidence that suggests that cancer cells use EV transmitted nucleic acids and proteins as a way of enacting an immune escape.…”

The exosomes in tumor immunity

“…Okoye et al found that Tregs could suppress effecter T cells by delivering miRNAs via exosomes. 58 Treg-derived exosomes contained premature and mature miRNAs, particularly with proapoptotic or anti-proliferative functions. These miRNAs could inhibit Ptgs2, thus limiting Th1 cell-associated responses.…”