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.

The pronounced inability of adult human/mammalian heart to regenerate causes millions of deaths following cardiac insult, particularly in the longer term. The extent and persistence of associated inflammation has been generally linked with adverse cardiac outcomes, including fibrosis, hypertrophy, and dysfunction. However, characteristics of the inflammatory response e.g. the maturity of resident macrophages and/or the activation status of infiltrating cells may differentially influence cardiac fibroblasts and, most importantly, cardiomyocytes, thus affecting cardiac regeneration, hypertrophy, fibrosis and dysfunction. Unraveling crucial parameters of such interactions in appropriate biological systems should confer decisive intervention potential in a serious health problem. In the past years we have studied in detail cellular and molecular players regulating pivotal events initiating or sustaining the progress to heart failure (HF) in mice and zebrafish and we propose here to combine the systems to globally study these interactions.