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INTERCOM Report Summary

Project ID: 337581
Funded under: FP7-IDEAS-ERC
Country: Netherlands

Mid-Term Report Summary - INTERCOM (Communication between immune cells via release of RNA-carrying vesicles: Lessons from viruses)

Communication between immune cells via release of RNA-carrying vesicles:
Lessons from viruses

Intercellular communication drives and regulates many physiological processes in multicellular organisms. In the last decade a new research field has rapidly developed, addressing the role of nano-sized vesicles in cellular communication. The vesicles contain unique combinations of lipids, proteins and genetic material, which serve to target the vesicles to specific cells and deliver the appropriate messages.
The INTERCOM project aims at understanding how cells of the immune system use extracellular vesicles (EV) to transfer genetic information to other cells and how this contributes to regulation of immune responses. A clear parallel can be drawn between these vesicles and enveloped viruses, which also aim to efficiently pass on genetic material to other cells via small vesicles. From recent publications it has now become clear that also naked viruses can disseminate via extracellular vesicles. There is obviously reason enough to learn from the mature field of virology to study the formation and function of extracellular vesicles.

In the initial phase of the project we invested in developing viral and cellular test systems to address similarities in mechanisms for intercellular gene transfer between viruses and EV. One of our starting points was to address whether stimuli imposed on cells by the microenvironment affect the molecular composition and function of extracellular vesicles. Cells of the immune system strongly adapt their function in response to signals from pathogens or the tissue environment. Certain environmental cues are known to dampen immune cell function, and we discovered that imposing such stimuli on immune cells induced the release of vesicles that inhibited the production of defined pro-inflammatory cytokines. We expect that this type of extracellular vesicles communicates signals to induce local immune suppression, which could aid in protecting tissues from potentially harmful inflammatory responses. At the molecular level, we found that environmental stimuli determined which types of microRNAs, a well-known family of gene regulatory small RNAs, were present in the vesicles. Interestingly, we also found that functionally different vesicle types also differed in the incorporation of other, highly-conserved, small non-coding RNAs with potential gene regulatory functions. In the next phase of the project, these data fuel further research on the mechanism behind selective incorporation of different RNA biotypes into extracellular vesicles and viruses and how these RNAs contribute to the function of these particles.

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