NCCR RNA& Disease - NCCR RNA & Disease: The role of RNA in disease mechanisms

The NCCR ‘RNA & Disease’ is a research instrument of the Swiss National Science Foundation, and is a coordinated, interdisciplinary research program aiming at identifying disease mechanisms resulting from aberrant RNA functions.

Silvia Monticelli will participate to this network with a project about the role of microRNAs (miRNAs) in the regulation of human T cell activation and functions in multiple sclerosis (MS). This project will be performed in collaboration with Prof. Jonathan Hall (ETH Zurich).

MS is a chronic neuroinflammatory disease initiated by autoreactive T lymphocytes; however, the frequency of circulating autoreactive lymphocytes is similar between people with MS and healthy individuals and, at least in animal models, it is also comparable to the frequency of T cells specific for foreign viruses, indicating that the mere presence of such autoreactive cells is not sufficient to explain their pathogenicity. Mechanisms likely to be crucial in MS include therefore all those processes that regulate the threshold, magnitude and quality of T lymphocyte responses. Among the factors that are gaining importance in the control of T cell responses in normal and diseased conditions are miRNAs, short noncoding RNA molecules that have become clear determinants of cellular fate and responses in a wide variety of different systems. MiRNAs are now considered increasingly important in autoimmunity, and similarly to infectious diseases, for which miRNAs are already in clinical trial, they could be potentially considered as a novel therapeutic strategy. However, due to the complex interactions usually existing between miRNAs and their targets, it is essential to first dissect the effects of a given miRNA network, which is exactly the scope of this project.