Extracellular vesicles’ transcriptomics: unravelling the role of short non-coding RNAs in autoimmunity

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It is estimated that over 36 million Europeans suffer from an autoimmune disease (AID) and according to the European League against Rheumatism one third of people of all ages are affected at some point during their lifetime. AIDs are a significant clinical problem, however, most of the current therapies target the terminal phase of inflammation and do not suppress the fundamental events responsible for the initiation of the autoimmune process. The EXAUTOIMMUNE project will use Sjögren’s syndrome (SS), one of the most common AIDs, as a model to create innovating strategies for dissecting the fundamental processes involved in the initiation of the autoimmune response. By using state-of-the-art nanotechnology we will characterize the extracellular vesicles (EV) secreted by the salivary gland epithelial cells, the main target of autoimmune responses in SS, and test their immunoregulatory properties. Then, we will apply next-generation sequencing to analyze the EVs’ RNA content and identify candidate RNA molecules that can be functionally tested for disruption of autoimmune processes. Linking EVs and extracellular RNA to autoimmunity is a fundamental theme of the current knowledge. The results of the proposed research will substantially add to the delineation of the biological relevance of extracellular RNA in modulating the regulatory mechanisms leading to autoimmunity. This study will form the foundation for transitioning from human biology to a mouse model, where the potential therapeutic value of EV and/or RNA-targeting will be tested, thus opening the best career opportunities for the applicant as a leader in this newly emerging landscape. Spearheading this research using next-generation tools and ideas will produce long-term synergies and will define EU and ERA as world leaders in the battle against AID. Collectively, the project activities will open the best career opportunities for the candidate, while advancing EU’s scientific competitiveness and innovation.