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Review
. 2014 Oct 29:5:542.
doi: 10.3389/fimmu.2014.00542. eCollection 2014.

"Small Talk" in the Innate Immune System via RNA-Containing Extracellular Vesicles

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Review

"Small Talk" in the Innate Immune System via RNA-Containing Extracellular Vesicles

Susanne G van der Grein et al. Front Immunol. .

Abstract

A newly uncovered means of communication between cells involves intercellular transfer of nano-sized extracellular vesicles (EV), composed of lipids, proteins, and genetic material. EV released by cells of the immune system can play a regulatory role in the induction and suppression of immune responses. These functions may be mediated not only by the bioactive lipids and proteins present in EV but also by EV-associated RNAs. The RNA in EV mainly consists of microRNAs and a large range of other small non-coding RNA species. Since many of these small RNAs have the potential to regulate gene expression, intercellular transfer of these RNAs via EV may cause long-term changes in the function of EV-targeted cells. Several types of innate immune cells release EV that affect innate immune responses and other (patho)physiological processes. Additionally, the innate immune system is influenced by EV released by non-immune cells and EV found in body fluids. In this review, we focus on how EV-associated RNAs contribute to these immune regulatory processes.

Keywords: exosomes; extracellular vesicles; infection; innate immune system; microRNA.

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Figures

Figure 1
Figure 1
Formation of RNA-containing EV. In mammalian cells, subpopulations of EV arise in different subcellular compartments. The different types of EV include exosomes, which are released upon fusion of MVB with the plasma membrane, and microvesicles that pinch off directly from the plasma membrane. Depicted are the RNA species detected in EV, i.e., short-non-coding RNAs (e.g., miRNA and tRNA fragments), long-non-coding RNAs, structural RNAs (e.g., Vault RNA and SRP-RNA), and protein-coding mRNAs. It is currently unknown whether all EV contain RNA and whether differences exist in the RNA content of various EV subpopulations. Various studies indicate that selective RNAs are enriched in EV (red), whereas others are preferentially retained in the cell (blue). This RNA sorting process may depend on specific motifs in the RNA sequence and/or may involve the action of RNA-binding proteins (e.g., the ribonucleoprotein A2B1) in addition to yet unidentified mechanisms.

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