Inflammation, RNA stability, therapeutics
Different autoimmune diseases often have similar mechanisms that trigger and drive the pathology. Therefore, it’s logical that having one autoimmune disorder increases the risk of acquiring another one. At the same time, autoimmune disease cooccurrence is rare. Our research found that type 1 diabetes (T1D) and multiple sclerosis (MS) share common mechanisms. We pinpointed the protein, called NLRX1, that protects against both autoimmune diseases. This protein belongs to the class of pattern recognition receptors that we use to detect pathogens. Unlike most of the pathogen recognition receptors that activate immunity, NLRX1 inhibits major proinflammatory pathways. We found that mice lacking this gene develop spontaneous neurological disorder similar to MS. Also, these mice develop spontaneous diabetes. These striking results that NLRX1 plays a central role in the development of autoimmunity. Accordingly, we designed this application to dissect cellular and molecular mechanisms that lay behind NLRX1-dependent protections. Also, we will discover which immune compartment benefits the most from the presence of NLRX1. Finally. we will develop new anti-inflammatory treatment augmenting NLRX1-dependent molecular pathways. Our studies will include the use of contemporary in vivo and in vitro assays and cutting-edge RNA stabilization techniques.