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

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

It is estimated that over 36 million Europeans suffer from some autoimmune disease (AID) and this represents the second cause of illness and the third cause of social security disability, after heart disease and cancer. In fact, according to the European League against Rheumatism (EULAR) one third of people of all ages are affected at some point during their lifetime. AID are a significant clinical problem because of their chronic nature and are thought to be associated with a failure of regulatory mechanisms. However, most of the current therapies target the terminal phase of inflammation and do not address the fundamental events responsible for the initiation and progression of the autoimmune process. Tackling these diseases at their source will require an understanding of how the abnormal immune reactions arise, how they are sustained, and the intrinsic mechanisms used to suppress these responses in healthy individuals. In this sense, research efforts should focus on better understanding of the molecular and cellular basis of AID for the development of curative and preventive strategies. EXAUTOIMMUNE project uses Sjögren’s syndrome (SS) as a model disease to create innovating strategies for addressing the fundamental processes involved in the initiation of the autoimmune responses. SS is a rather common systemic autoimmune disease, as common as Rheumatoid Arthritis. Salivary gland epithelial cells (SGEC) in SS lesions are active participants in the induction and perpetuation of the inflammatory process, from early onset to chronic state of the disease. Extracellular vesicles (EVs), including exosomes, microvesicles and apoptotic bodies, are secreted by almost all cell types and mediate intercellular communication acting as nanoshuttles and transfering information among cells. EVs contain various classes of short non-coding RNAs of approximately 20-35 nucleotides in length. They can act as regulators of gene function, and are emerging as pivotal regulators of immune responses. The OVERALL OBJECTIVE of the EXAUTOIMMUNE project is to define the immunomodulatory function of EVs and their RNA-cargo in SS. We hypothesize that SGEC through the secretion of RNA-containing EVs, modulate the regulatory mechanisms in favor of autoimmunity.

Data: CORDIS, © European Union