Decoding genetic messages in extracellular vesicles released by immune cells - lessons for biomarker applications

Extracellular vesicles (EV) are 50 – 1000 nanometer-sized membrane-enclosed vesicles that are released by virtually all cells. EV shuttle proteins, lipids and RNA between cells, and thereby contribute to intercellular communication. Changes in the condition of cells, such as during immune-activation or during disease, can lead to changes in the composition of the EV released by these cells and the effects that these EV have on recipient cells. EV in body fluids are in the limelight as disease biomarkers, since they contain molecular information on the (disease)status of their parental cells. It is thought that the RNA content of EV is a ‘snapshot’ of the cellular transcriptome. EV contain various types of non-coding RNA, of which many are involved in the regulation of transcription and translation processes. Of these RNA types, microRNAs have been studied most intensively. Using various immune cells, we investigated whether cellular activation influences the levels of other non-coding RNAs in EV. Besides expected changes in microRNA content, we additionally detected changes in the Y-RNA content of EV of activated immune cells. Our results indicated that Y-RNA may contribute to the communication between immune cells, and that EV from different immune cells contain unique Y-RNA signatures. Furthermore, we found that systemic inflammation leads to changes in EV-associated Y-RNA levels in human plasma. The analysis of Y-RNA signatures in plasma may potentially be used for detection and monitoring of inflammatory conditions such as sepsis and rheumatoid arthritis.